Systems and methods for delivering microdoses of medication

ABSTRACT

Devices, systems, and methods are provided herein for delivering medication (e.g., insulin) via a wearable pump having a patch-style form factor for adhesion to a user&#39;s body. The reusable pump may be coupled to a disposable cap housing a microdosing system for delivering precise, repeatable doses of medication to a cannula configured to deliver medication to a target infusion area beneath the user&#39;s outer skin layer. The system further may include an applicator for inserting the cannula into the user&#39;s skin and/or applying an adhesive pad to the skin.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/652,463, filed Feb. 24, 2022, now U.S. Pat. No. 11,712,514, whichclaims the benefit of priority of U.S. Provisional Patent ApplicationNo. 63/195,564, filed Jun. 1, 2021, the entire contents of each of whichare incorporated herein by reference.

TECHNICAL FIELD

The technology relates to systems and methods for delivering medicationsuch as insulin to a user, for example, wearable insulin pumps having apatch-style form factor for adhesion to a user's body surface andaccessories for applying and managing the same.

BACKGROUND

Wearable insulin pumps are known for providing a Type I DiabetesMellitus patient with small doses of short acting insulin continuously(basal rate). The device also is used to deliver variable amounts ofinsulin when a meal is consumed (bolus). The basal insulin rates areusually programmed in a pump by a physician, and one or multiple basalsettings may be programmed in the pump based on the patient's needs. Thepatient may program the amount of insulin for mealtime bolus directly onthe pump. Most pumps also include bolus calculators to help the patientdetermine the amount of insulin the patient may need at mealtime basedon the patient's glucose levels and the amount of carbohydrates thepatient may consume. The objective is to control the patient's bloodglucose level within a desired range. Some such insulin pumps arecoupled to an adhesive patch that permits the pump to be directlyadhered to a user's body surface, for example the abdomen, and arereferred to as “patch pumps.” In addition, some previously known systemswere configured to interface wirelessly with a continuous glucosemonitor, which typically also may be disposed on a patch designed to beadhered to the user's body. Other previously known systems employ stillfurther modules designed to monitor user activity and report thatactivity to a controller associated with the patch pump to titrate theinsulin delivery in accordance with the user's activity level.

WO 02/20073 describes an ambulatory patch pump for delivering insulin tomanage diabetes. The pump is part of a system that includes the fluiddelivery device, a separate, remote control device, and accessories fortranscutaneous delivery of fluid medications.

U.S. Pat. No. 7,879,026 describes an infusion pump that is designed tobe wearable, e.g., on a user's belt, and is coupled to an infusioncannula that extends through and is fixed to a user's skin using anadhesive patch. The infusion pump may include an accelerometer or othermotion sensor to detect the user's activity level, the output of whichmay be used to automatically adjust a rate of insulin infusion to theuser based at least in part on a detected activity level of the user.

U.S. Pat. No. 9,735,893 describes a patch system for in-situ therapeutictreatment wherein a plurality of biological parameter monitoring devicesmay be disposed on separate stretchable patches designed to adhere to auser's skin. The monitoring devices communicate with each other, andother therapeutic devices, via short-range wireless, such as Bluetooth.The patent describes that patch-based monitoring devices may beconfigured to communicate to a belt-worn insulin pump, and that onepatch-based monitoring device may include pulse oximetry electronics formeasuring blood volume. The patent does not describe a patch-basedinsulin pump and requires intercommunication between its variouscomponents, providing a potential failure mode.

U.S. Patent App. Pub. No. 2018/0339102, the entire contents of which areincorporated herein by reference, assigned to the assignee of theinstant application, describes a self-contained patch pump having amotor-actuated syringe together with a microdosing pump chamber.

WO 2019/110839, the entire contents of which are incorporated herein byreference, assigned to the assignee of the instant application,describes a drug delivery device comprising a pumping system and aliquid reservoir fluidly connected to a delivery system outlet. Theliquid reservoir has an elastic plunger sealingly slidable within acontainer wall of the liquid reservoir for expelling liquid out of thereservoir.

There exists a need for systems and methods for delivering medicationsuch as insulin that are user-friendly, environmentally-friendly, lowercost, discreet, less prone to errors, and/or that deliver precise,repeatable doses of medication.

SUMMARY

Provided herein are systems and methods for delivering medication, suchas insulin, that are user-friendly, environmentally-friendly, lowercost, discreet, less prone to errors, and/or that deliver precise,repeatable doses of medication, as well as accessories for applying andmanaging the same. In a preferred embodiment, the system includes awearable insulin pump having a patch-style form factor for adhesion to auser's body surface.

In accordance with one aspect, a medication infusion system is providedthat includes a patch pump configured to be removably adhered to awearer's skin for delivering doses of medication (e.g., insulin). Forexample, the doses of medication may be delivered from a cartridge(e.g., a pre-filled cartridge) through a transcutaneous portion. Thetranscutaneous portion may include a cannula and/or needle configured tobe fluidically coupled to the cartridge. The patch pump may include apump housing configured to house a controller, a rechargeable battery,and/or a pump motor configured to pump the medication towards thetranscutaneous portion. Further, a cap may be included that isconfigured to be removably coupled to the pump housing. The cap andcartridge may be disposable after the doses of medication are deliveredfrom the pre-filled cartridge while the patch pump may be reusable withadditional caps and pre-filled cartridges.

The medication infusion system may include a charging station configuredto charge the rechargeable battery when the patch pump is coupled to thecharging station. The pump housing may include a first inductive coilcoupled to the rechargeable battery and the charging station may includea second inductive coil. In some embodiments, the second inductive coilemits power to the first inductive coil. The medication infusion systemmay include a wireless communication chip within the pump housingconfigured to wirelessly communicate data to and from the patch pump.

The medication infusion system may include an adhesive pad configured tobe removably adhered to the wearer's skin to couple the patch pump tothe wearer. The adhesive pad may include one or more pad clips holes andthe pump and cap assembly (e.g., at lateral sides of the cap) mayinclude one or more cap clips sized and shaped to fit within the one ormore pad clips holes. In this manner, the pump and cap assembly may belocked to the adhesive pad for secure coupling of the patch pump to thewearer's skin. The cap further may include one or more unclippingbuttons coupled to the one or more cap clips. When pressed, theunclipping buttons, may deflect the one or more cap clips such that theone or more cap clips uncouple from the one or more pad clips holes.Thus, the pump and cap assembly may be easily unlocked from the adhesivepad by the wearer in a user friendly manner.

The patch pump and the cap may not include a reservoir to hold multipledoses of medication separate from the pre-filled cartridge.Advantageously, in such embodiments, there is no need toinject/introduce medication from an insulin cartridge into a reservoirin the patch pump like some commercially available devices. Instead, thepatch pump works seamlessly with a pre-filled cartridge, which is easieron the user. The pump housing and the cap, when coupled together, maycompletely encase the pre-filled cartridge.

The transcutaneous portion may include a cannula configured to extendinto the wearer's skin. The cannula may have one or more aperturesbeneath the outer skin layer for delivery of the dose of medication. Thetranscutaneous portion may include a needle configured to be fluidicallycoupled to the cannula.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The medication infusion system may include a pump motordisposed within a pump housing, the pump motor configured to pump themedication towards the transcutaneous portion. The medication infusionsystem further may include a sensor configured to sense a parameter, avibration motor separate from the pump motor, and a controlleroperatively coupled to the sensor and the vibration motor. The sensormay be disposed in a housing separate from the pump housing.

The controller may be configured to cause the vibration motor to vibrateto alert the wearer based on the parameter sensed by the sensor, forexample, when the sensed parameter falls outside a predeterminedthreshold. The controller further may be configured to determine that anerror has occurred associated with operation of the patch pump based onthe sensed parameter to cause the vibration motor to vibrate based onthe determination of the error.

For example, the sensor may be configured to sense a pressure within thecartridge and the controller may be configured to cause the vibrationmotor to vibrate when the pressure within the cartridge falls outside apredetermined pressure range. The medication infusion system further mayinclude a dosing tube disposed within the pump housing and the dosingtube may be configured to receive medication from the cartridge. Thesensor may be configured to detect an occlusion within the dosing tubeor the transcutaneous portion and the controller may be configured tocause the vibration motor to vibrate when the sensor detects informationindicative of an occlusion within the dosing tube or the transcutaneousportion. Alternatively, the controller is configured to cause thevibration motor to vibrate only when the sensor detects repeatedocclusions.

The sensor may be configured to monitor glucose levels of the wearer andthe controller may configured to cause the vibration motor to vibratewhen the wearer's glucose level falls outside a predetermined glucoselevel range. Alternatively, the sensor may be a photoplethysmographicmodule configured to sense at least one of the wearer's heart rate orphysiologic parameters and the controller may be configured to cause thevibration motor to vibrate when the at least one of the wearer's heartrate or physiologic parameters fall outside a predeterminedphotoplethysmographic threshold. In another embodiment, the sensor maybe an accelerometer and the sensed parameter may be associated with thewearer's activity level. The controller may be configured to cause thevibration motor to vibrate when the wearer's activity level is outside apredetermined threshold. In another embodiment, the sensor may beconfigured to detect a temperature within the patch pump and thecontroller may be configured to cause the vibration motor to vibratewhen the temperature falls outside a predetermined range.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The medication infusion device further may include a pusher anda pump motor disposed within a pump housing and a sensor. The pump motormay be coupled to the pusher and may be configured to move the pusher tomove the medication in the cartridge towards the transcutaneous portion.

The sensor may be configured to sense a position of the pusher withinthe pump housing to indicate a state of the patch pump. The position ofpusher may also indicate that the pusher transitioned to a firstposition such that the cartridge is permitted to be removed andexchanged for a subsequent cartridge. The sensor may be a contact sensorthat senses the position of the pusher based on contact with a componentof the pusher.

The medication infusion device further may include a controller disposedwithin the pump housing and operatively coupled to the pump motor andthe sensor. The controller may execute instructions, which indicate thata battery within the patch pump is charged to a power level sufficientto empty the medication from the cartridge based on the position of thepusher sensed by the sensor. The controller further may be configured tocause the component to move in an opposite direction after sensingcontact with the component, for example, to a home position.

The medication infusion device further may include a cap configured tobe locked to the pump housing during delivery of the doses ofmedication. The position of the pusher may indicate that the cap ispermitted to be unlocked from the pump housing for removal of thecartridge. In addition, a level of battery charge further may indicatethat the cap is permitted to be unlocked. The medication infusion devicemay include a second sensor configured to monitor the level of batterycharge.

In accordance with another aspect, a component for use in a medicationinfusion device, is provided. The component may be a cap configured tobe removably coupled to a pump housing of the patch pump. The componentmay be configured to measure and deliver a predetermined dose ofmedication to the wearer. The component may include a dosing tubeconfigured to receive medication, a plurality of levers configured tocontact the dosing tube to move a predetermined dose of medicationtowards the transcutaneous portion, and a circular cam. The circular cammay include a shaft oriented in a first plane and a circular plateoriented in a second plane, the first and second plane may beorthogonal. The circular plate may be coupled to the shaft and mayinclude surfaces configured to move the plurality of levers in a seriesof steps upon rotation of the shaft. The rotation of the shaft maydeliver the predetermined dose of medication towards the wearer.

The plurality of levers may include a first lever disposed on a firstportion of the dosing tube, a second lever disposed on a second portionof the dosing tube, and a middle lever disposed adjacent to a reservoirportion (e.g., a compartment) between the first portion and the secondportion. The reservoir portion may be configured to hold thepredetermined dose of medication. The first portion, second portion, andreservoir portion of the dosing tube are disposed on a flattened portionof the dosing tube. The reservoir portion of the dosing tube may includeone or more welded portions that are configured to increase the accuracyof the volume within the reservoir.

The plurality of levers may be independently movable and configured tosequentially transition from a raised position to a lowered position.The raised position may permit medication to flow from the cartridgetowards the transcutaneous portion and the lowered position may positionthe plurality of levers in contact with the dosing tube such thatmedication is prevented from flowing from the cartridge towards thetranscutaneous portion.

The plurality of levers may move in a predetermined sequence of stepsconfigured to deliver the predetermined dose of medication to thewearer. The first lever may be configured to move to a raised position,the middle lever may be configured to move to a raised position, and,after the middle lever moves to the raised position, the first lever maybe configured to move to a lowered position such that the predetermineddose of medication is disposed within the reservoir portion. After thefirst lever moves to the lowered position, the second lever may beconfigured to move to a raised position, the middle lever may beconfigured to move to a lowered position, and the second lever may beconfigured to move to a lowered position such that the predetermineddose of medication is delivered towards the wearer.

The first lever may include a first extended arm having a first rampedportion, the second lever may include a second extended arm having asecond ramped portion, and the middle lever may include a middleextended arm having a middle ramped portion. The first, second, andmiddle ramped portions may be configured to contact the surfaces of thecircular cam, which may include a first surface and a second surface.The first lever may transition from a lowered position to a raisedposition when the first ramped portion contacts the first surface of thecircular cam, the second lever may transition from a lowered position toa raised position when the second ramped portion contacts the firstsurface of the circular cam, and the middle lever may transition from alowered position to a raised position when the middle ramped portioncontacts the second surface of the circular cam.

The first surface may be sized and shaped such that the first surface isdisposable between the first ramped portion and the second rampedportion without contacting the first ramped portion or the second rampedportion. The first second surface of the circular plate and the first,second, and middle ramped portions of the plurality of levers mayinclude rounded edges such that the noise from rotation of the circularcam is minimized.

The first surface of the circular cam may be positioned radially outwardof the second surface of the circular cam. The surfaces on the circularplate may include a third surface and a fourth surface that mirror thefirst surface and the second surface, respectively. During a 360 degreerotation of the circular cam, contact between the first and secondsurfaces and the plurality of levers may move the predetermined dose ofmedication to the wearer. Contact between the third and fourth surfacesand the plurality of levers may move a second predetermined dose ofmedication to the wearer. A 180 degree rotation of the shaft may deliverthe predetermined dose of medication and another 180 degree rotation ofthe shaft may deliver a second predetermined dose of medication havingthe same volume of medication as the predetermined dose.

The transcutaneous portion may include a cannula configured to extendinto the wearer's skin. The cannula may have one or more aperturesbeneath the outer skin layer for delivery of the dose of medication. Thetranscutaneous portion may include a needle configured to be fluidicallycoupled to the cannula. The needle may be configured to extend from thedosing tube to the cannula.

A method for delivering doses of medication is also provided, the methodincluding providing a patch pump having a dosing tube, a plurality oflevers, and a circular cam, as described above, and rotating the shaftof the circular cam. Rotating the shaft may cause the circular cam torotate such that the surfaces contact the plurality of levers duringrotation to cause the plurality of levers to move in a predefinedpattern to selectively open and close sections of the dosing tube todeliver the predetermined dose of medication transcutaneously to thewearer. Rotating the shaft further may cause at least one lever of theplurality of levers to transition from a lowered position to contact thedosing tube such that medication is prevented from flowing from thecartridge towards the transcutaneous portion to a raised position suchthat medication flows from the cartridge towards the transcutaneousportion.

The plurality of levers may include a first lever disposed on a firstportion of the dosing tube, a second lever disposed on a second portionof the dosing tube, and a middle lever disposed adjacent to a reservoirportion between the first portion and the second portion, the reservoirportion configured to hold the predetermined dose of medication. Thefirst lever may include a first extended arm having a first rampedportion, the second lever may include a second extended arm having asecond ramped portion, and the middle lever may include a middleextended arm having a middle ramped portion. The first, second, andmiddle ramped portions may be configured to contact the surfaces of thecircular cam.

Rotating the shaft may cause the first lever to transition to the raisedposition, the middle lever to transition to the raised position, and,after transitioning the middle lever to the raised position, the firstlever to transition to the lowered position such that the predetermineddose of medication is disposed within the reservoir portion. Rotatingthe shaft further may cause, after transitioning the first lever to thelowered position, the second lever to transition to the raised position,after transitioning the second lever to the raised position, the middlelever to transition to the lowered position, and the second lever totransition to the lowered position such that the predetermined dose ofmedication is delivered transcutaneously to the wearer.

The surfaces on the circular plate may include a first surface and asecond surface such that rotating the shaft further causes the firstramped portion to contact the first surface of the circular cam suchthat the first lever transitions from a lowered position to a raisedposition, the second ramped portion to contact the first surface of thecircular cam such that the second lever transitions from a loweredposition to a raised position, and the middle ramped portion to contactthe second surface of the circular cam such that the middle levertransitions from a lowered position to a raised position.

The surfaces on the circular plate may include a third surface and afourth surface that mirror the first surface and the second surface,respectively, such that rotating the shaft 360 degrees causes the firstand second surfaces to contact the plurality of levers such that thepredetermined dose of medication is delivered to the wearer and thethird and fourth surfaces to contact the plurality of levers such that asecond predetermined dose of medication is delivered to the wearer.Further, rotating the shaft 180 degrees may deliver a predetermined doseof medication and rotating the shaft another 180 degrees may deliver asecond predetermined dose of medication having the same volume ofmedication as the predetermined dose.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The patch pump may include a pump housing and a cap housingconfigured to be locked together to hold the cartridge. The medicationinfusion device further may include a rechargeable battery disposedwithin the pump housing and a controller configured to monitor batterylife of the rechargeable battery. The controller may be configured tounlock the pump housing from the cap housing based on determining thatthe battery life has been charged to a predetermined state.

The medication infusion device further may include a pusher disposedwithin the pump housing. The pusher may be configured to push medicationout of the cartridge during pumping. The controller, upon determiningthat the battery life has been charged to a state below full charge, maycause the pusher to move from an empty position to a full positionwithin the pump housing. The state below full charge may be apredetermined time before battery life sufficient to empty themedication from the cartridge.

The pusher may include a component that, in the full position, contactsa contact sensor. The component of the pusher may include a nutconfigured to move along a thread of a screw. After contacting thecontact sensor, the component of the pusher may move to a home positionwherein the pusher does not contact the contact sensor. The controllermay be configured to only unlock the pump housing from the cap housingif the controller determines that the patch pump is in the homeposition.

The cap housing may include a tab and the pump housing may include amechanical coupling sized and shaped to receive the tab. The mechanicalcoupling and the tab may be configured to rotate upon movement of thepusher and may be oriented in a first direction when the pump housing islocked to the cap housing. The mechanical coupling and the tab may beoriented in a second direction, different from the first direction, whenthe pump housing is unlocked to the cap housing.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The medication infusion device further may include a pump motordisposed within a pump housing, a sensor, and a controller operativelycoupled to the pump motor and the sensor. The pump motor may beconfigured to pump the medication in the cartridge towards thetranscutaneous portion. The sensor may be configured to detect thewearer's skin, for example, by measuring capacitance, and to generateinformation to indicate detection of the wearer's skin. The controllermay be configured to cause the pump motor to activate only if theinformation indicates detection of the wearer's skin.

The sensor may be disposed on a first side of the pump housing and maybe configured to detect the wearer's skin on the first side. Themedication infusion device further may include a second sensor disposedon a second side of the pump housing, the second side different from thefirst side. The second sensor may be configured to detect the wearer'sskin on the second side. The controller may cause the pump motor toactivate only if the second sensor does not detect the wearer's skin. Byensuring that only one sensor detects the wearer's skin, this ensuresthat the patch pump does not deliver medication while the wearer isholding the patch pump.

The medication infusion device further may include aphotoplethysmography module. The controller may be configured to causethe pump motor to activate only if both the sensor and thephotoplethysmography module detect the wearer's skin. The sensor may beincorporated in a photoplethysmography module.

In accordance with another aspect, a component for use in a medicationinfusion device including a patch pump is provided. The component may beconfigured to complete an initialization process such that delivery ofmedication to the wearer is prevented until the pressure within thecartridge reaches a predetermined pressure range. The component mayinclude a dosing tube configured to receive medication, a plurality oflevers configured to contact the dosing tube to move a predetermineddose of medication towards the transcutaneous portion, and a camconfigured to move from an initialization position to a dosing position.In the initialization position, the cam may not be coupled to theplurality of levers such that movement of the cam does not causemovement of the plurality of levers and, in the dosing position, the cammay be coupled to the plurality of levers such that movement of the camcauses movement of the plurality of levers in a predetermined manner togenerate the predetermined dose of medication for delivery to thewearer.

The cam may include a shaft oriented in a first plane and a circularplate oriented in a second plane. The cam further may include a springconfigured to apply an upward force on the circular plate in theinitialization position. The shaft may include an outer shaft and aninner shaft disposed within the outer shaft. The outer shaft may includeat least one wing configured to transition to a position above thespring when the cam moves to the dosing position. The component furthermay include a microdosing structure configured to house at least aportion of the inner shaft and the outer shaft in the initializationposition. The microdosing structure may include at least one damperconfigured to interact with the at least one wing such that noise frommovement of the cam is reduced.

The cam may be configured to move from an initialization position to adosing position when the cam is moved in a first direction. In thedosing position, the cam may be configured to move the plurality oflevers when the cam is moved in a second direction, different from thefirst direction. During initialization, prior to moving from theinitialization position to the dosing position, the cam may beconfigured to move in the second direction. Movement of the cam in thesecond direction may prevent the cam from transitioning from theinitialization position to the dosing position. Movement of the cam inthe first direction may transition the cam from the initializationposition to the dosing position permanently without the ability to moveback to the initialization position.

The patch pump may include a sensor configured to sense a pressurewithin the cartridge and a controller operatively coupled to the sensor.The controller may be configured to cause the cam to move from theinitialization position to the dosing position when the pressure withinthe cartridge reaches a predetermined value, for example, a valuebetween 600 mbar and 900 mbar.

The transcutaneous portion may include a cannula configured to extendinto the wearer's skin. The cannula may have one or more aperturesbeneath the outer skin layer for delivery of the dose of medication. Thetranscutaneous portion may include a needle configured to be fluidicallycoupled to the cannula. The needle may be configured to extend from thedosing tube to the cannula. A distal end of the needle may be configuredto pierce a septum at a proximal region of the cannula and reside belowthe septum such that the septum fluidically seals the proximal region ofthe cannula around the needle.

A method for initializing a patch pump in preparation fortranscutaneously delivering doses of medication from a cartridge via thepatch pump is also provided. The method may include adhering the patchpump having a dosing tube and a plurality of levers, as described above,to a wearer's skin to permit transcutaneous delivery of the doses ofmedication. The method further may include moving a cam within the patchpump in an initialization position wherein the cam is not coupled to theplurality of levers such that movement of the cam does not causemovement of the plurality of levers. The method further may includemoving the cam from the initialization position to a dosing position andmoving the cam in the dosing position wherein the cam is coupled to theplurality of levers such that movement of the cam causes movement of theplurality of levers in a predetermined manner to generate thepredetermined dose of medication for delivery to the wearer.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The patch pump may include a pump housing and cap housingconfigured to be removably coupled to the pump housing. The medicationinfusion device further may include a dosing tube disposed within thecap housing and configured to be fluidically coupled to the cartridge toreceive the medication and to be fluidically coupled to thetranscutaneous portion, a pump motor disposed within a pump housing andconfigured to pump the medication in the cartridge towards the dosingtube and the transcutaneous portion, a sensor, and a controlleroperatively coupled to the pump motor and the sensor. The sensor may beconfigured to generate information indicative of pressure within thecartridge.

The controller may be configured to cause the pump motor, in aninitialization position, to activate to increase pressure within thecartridge while the dosing tube is closed such that the medicationcannot travel to the transcutaneous portion. The controller further maybe configured to determine that the pressure within the cartridge isabove a predetermined threshold based on the information from thesensor. For example, the predetermined threshold may be 600-900 mbar.The predetermined threshold may be selected such that the cartridge ispressurized to eliminate bubbles and the formation of bubbles in themedication. After the determination, the controller may be configured totransition the patch pump from the initialization position to a dosingposition to permit the dosing tube to open for medication to travel tothe transcutaneous portion.

The medication infusion device further may include a plurality of leversand a cam. The plurality of levers may be configured to contact thedosing tube to move a predetermined dose of medication towards thetranscutaneous portion. The cam may be configured to move from theinitialization position to the dosing position. In the initializationposition, the cam may not coupled to the plurality of levers such thatmovement of the cam does not cause movement of the plurality of levers.In the dosing position, the cam may be coupled to the plurality oflevers such that movement of the cam causes movement of the plurality oflevers in a predetermined manner to generate the predetermined dose ofmedication for delivery to the wearer.

The pump motor may be activated to pump in the initialization positionan amount of pumping greater than required for 10 doses of medication.The medication infusion device further may include a pusher coupled tothe pump motor and the cartridge. Responsive to activation of the pumpmotor, the pusher may push on the cartridge to increase the pressurewithin the cartridge to the predetermined threshold in theinitialization position. The pusher may push on the cartridge in thedosing position for a predetermined dose of medication to be deliveredto the wearer.

A method for initializing a patch pump in preparation fortranscutaneously delivering doses of medication from a cartridge via thepatch pump is also provided. The method may include adhering the patchpump to permit transcutaneous delivery of the doses of medication. Thepatch pump may include a dosing tube configured to receive themedication and a pump motor disposed within a pump housing andconfigured to pump the medication in the cartridge towards the dosingtube. The method further may include activating the pump motor, in aninitialization position, to increase pressure within the cartridge whilethe dosing tube is closed such that the medication cannot travel to thetranscutaneous portion. The method further may include sensinginformation indicative of pressure within the cartridge using a sensorand determining that the pressure within the cartridge is above apredetermined threshold based on the information from the sensor. Onlyafter determining that the pressure within the cartridge is above thepredetermined threshold, the patch pump may be transitioned from theinitialization position to a dosing position to permit the dosing tubeto open for medication to travel to the transcutaneous portion.

The patch pump further may include a cam and a plurality of leversconfigured to contact the dosing tube to move a predetermined dose ofmedication towards the transcutaneous portion. The method further mayinclude causing the cam to move from the initialization position to thedosing position, as described above. The pump motor may be activated, inthe initialization position, to increase pressure within the cartridgecomprises pressurizing the cartridge to reduce bubbles and the formationof bubbles in the medication.

The patch pump further may include a pusher coupled to the pump motorand the cartridge. The method may include causing the pusher to push onthe cartridge to increase the pressure within the cartridge to thepredetermined threshold in the initialization position. The methodfurther may include causing the pusher to push on the cartridge in thedosing position for a predetermined dose of medication to be deliveredto the wearer.

In accordance with another aspect, a method of making a component foruse in a medication infusion device is provided. The component may be aflattened dosing tube that may be used to measure a predetermined doseof medication. The method may include selecting a polymer tube sized forreceiving a dose of medication, flattening a portion of the polymertube, selecting a support, and welding the flattened portion of thepolymer tube to the support. Welding the flattened portion may includelaser welding and may create a reservoir sized for generating the doseof medication with a predetermined volume selected for delivery to thewearer, for example, 0.08-1 uL, 0.2-0.6 uL, or 0.2-0.3 uL.

The polymer tube may be transparent to a laser and the support may notbe transparent to the laser. The flattened portion may include a tubewall having a uniform thickness. The flattened portion may be flexiblesuch that when the medication has a predetermined pressure, thereservoir is sized to hold the predetermined volume of medication, whenthe medication has a pressure greater than the predetermined pressure,the reservoir is sized to hold a greater volume than the predeterminedvolume of medication, and when the medication has a pressure less thanthe predetermined pressure, the reservoir is sized to hold a lesservolume than the predetermined volume of medication.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The medication infusion device further may include a pumphousing configured to hold a pump and a controller and to receive thecartridge. The medication infusion device further may include a caphousing configured to be locked to the pump housing to lock thecartridge therebetween. The cap housing may include at least threeprotrusions radially spaced around a portion of the cap housingconfigured to receive the cartridge. The at least three protrusions maybe configured to engage corresponding receptacles in the pump housing tolock the cap housing to the pump housing.

The protrusions and receptacles may engage in a manner to resist acontinuous pushing force on the cap housing from the cartridge and toremain locked. The at least three protrusions may prevent a rotationgreater than 90 degrees. The at least three protrusions may include afirst protrusion that has a first portion having a wide engagement slitand a second portion having a narrower engagement slit.

The pump housing may be reusable and the cap housing may be disposable.The pump housing may include a first material and the cap housing mayinclude a second material. The first material may have a greater creepresistance and/or a greater thickness than the second material. The pumphousing may be designed to have a greater creep resistance such that thecap housing fails, or deforms, before the pump housing fails or deforms.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The medication infusion device further may include a dosingtube configured to receive medication, a plurality of levers configuredto contact the dosing tube to move a predetermined dose of medicationtowards the transcutaneous portion, a sensor configured to senseposition of one or more of the plurality of levers, and a controlleroperatively coupled to the sensor. The sensor further may be configuredto sense displacement of one or more of the plurality of levers. Thecontroller may be configured to sense an infusion anomaly (e.g., anocclusion) associated with medication delivery from the dosing tubebased on the sensed displacement from the sensor. This method ofmonitoring the dosing tube provides fast occlusion detection within thepatch pump. Alternatively, the pump may be configured to house thesensor, a cap may be configured to house the plurality of levers, andthe controller may configured to sense whether the pump is coupled tothe cap based on the sensed position of the one or more of the pluralityof levers.

The dosing tube may include a flattened portion configured to hold thepredetermined dose of medication. The plurality of levers may include afirst lever disposed on a first side of the flattened portion, a secondlever disposed on a second side of the flattened portion, and a middlelever disposed adjacent to the flattened portion. The plurality oflevers may be configured to sequentially transition from a raisedposition such that medication can flow from the cartridge to thetranscutaneous portion to a lowered position to contact the dosing tubesuch that medication is prevented from flowing from the cartridge to thetranscutaneous portion.

The sensor may include a hall-effect sensor configured to detectmovement of a magnet coupled to one of the plurality of levers. Forexample, the hall-effect sensor may be configured to detect movement ofa magnet coupled to the middle lever. The controller may sense theinfusion anomaly if the sensed displacement is outside a threshold rangeas determined based on proximity of the magnet to the hall-effect sensorover time. The controller further may sense the infusion anomaly usingan algorithm based on the displacement of the magnet to the hall-effectsensor during an injection cycle. The controller may be configured tocause the medication infusion device to vibrate to alert the wearerbased on the sensed infusion anomaly. Alternatively, the controller maysense that the medication infusion device is not delivering medicationif the sensor does not sense a displacement of the one or more of theplurality of levers. The sensor may further be configured to senseinformation indicative of the presence or absence of the cap and/or todetermine a status of the cap. For example, the information from thesensor may be used to determine whether cap has been used or whether thecap is new. The information may be based on the strength of the magneticfield from a magnet within the cap, as the strength of the field willchange based on the position of the magnet in the cap. In someembodiments, the magnet changes position in the cap from theinitialization position to the dosing position.

A method for monitoring transcutaneous delivery of doses of medicationis also provided, the method including delivering doses of medicationusing a patch pump adhered to a wearer's skin. The patch pump mayinclude a dosing tube configured to receive the medication responsive topumping and a plurality of levers configured to contact the dosing tube.The patch pump further may include a transcutaneous portion fluidicallycoupled to the dosing tube. The dosing tube may include a flattenedportion configured to hold the predetermined dose of medication and theplurality of levers may include a first lever disposed on a first sideof the flattened portion, a second lever disposed on a second side ofthe flattened portion, and a middle lever disposed adjacent to theflattened portion. Delivering doses of medication may includesequentially transitioning one or more of the plurality of levers from araised position such that medication can flow from the cartridge to thetranscutaneous portion to a lowered position to contact the dosing tubesuch that medication is prevented from flowing from the cartridge to thetranscutaneous portion.

The method further may include sensing displacement of one or more ofthe plurality of levers during the pumping and determining an infusionanomaly associated with medication delivery from the dosing tube hasoccurred based on the sensed displacement of the one or more of theplurality of levers. Sensing displacement of one or more of theplurality of levers may include detecting movement of a magnet coupledto one of the plurality of levers. Determining that the infusion anomalyhas occurred may include determining that the dosing tube or thetranscutaneous portion is occluded.

In some embodiments, a magnet may be coupled to the middle lever. Themethod may include determining if the sensed displacement is outside athreshold range as determined by the proximity of the magnet to thesensor over time. Sensing the infusion anomaly may include using analgorithm based on displacement of the magnet to the hall-effect sensorduring an injection cycle. The method further may include sensing thatthe patch pump is not delivering medication if the sensor does not sensea predetermined displacement of the one or more of the plurality oflevers.

The patch pump further may include a pump configured to house the sensorand a cap configured to house the plurality of levers. The method mayinclude sensing whether the pump is coupled to the cap based on thesensed displacement of the one or more of the plurality of levers and/ordetecting the status of the cap, for example, whether the cap is new orused.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The medication infusion device further may include a pumphousing, a pump motor disposed within the pump housing, at least onesensor disposed within the pump housing, one or more processors, and awireless communication chip disposed within the pump housing.

A first processor may be disposed within the pump housing and configuredto execute first programmed instructions stored in a first memory tocause the pump motor to pump the medication towards the transcutaneousportion and to monitor sensed parameter generated by the at least onesensor. A second processor may be disposed within the pump housing andconfigured to execute second programmed instructions stored in a secondmemory to communicate data to and from the patch pump via the wirelesscommunication chip. The first processor may be configured such that itcannot receive data from outside the patch pump, enhancing the securityof the medication infusion device. The first programmed instructions mayinclude class C software and the second programmed instructions mayinclude class B software. The first processor may be an autonomous, realtime state machine.

At least one sensor may be configured to sense a pressure within thecartridge or to detect an occlusion within the transcutaneous portion.The at least one sensor may include a sensor disposed on a first side ofthe pump housing and configured to detect the wearer's skin. The firstprocessor further may be configured to execute first programmedinstructions stored in the first memory to cause the pump motor to pushthe medication in the cartridge towards the transcutaneous portion onlywhen the sensor detects the wearer's skin.

The patch pump further may include a pump housing and a cap housingconfigured to be locked together to hold the cartridge. A rechargeablebattery may be disposed within the pump housing. The first processorfurther may be configured to execute first programmed instructionsstored in the first memory to monitor battery life of the rechargeablebattery and to cause the pump housing to unlock from the cap housingwhen the first processor determines that the battery life has beencharged to a predetermined state.

In another embodiment, at least one sensor is configured to sense theposition of the pusher to indicate that the cartridge is permitted to beremoved and exchanged for a subsequent cartridge. The first processorfurther may be configured to execute first programmed instructionsstored in the first memory to cause a position of a pusher coupled tothe pump motor to move to a home position and to cause the pump housingto unlock from the cap housing only when the first processor determinesthat the pusher is in the home position.

In another embodiment, the at least one sensor may be configured tosense a position of a circular cam including a shaft configured torotate to deliver a predetermined dose of medication. The sensedposition may indicate that a dosing cycle is complete. The firstprocessor further may be configured to execute first programmedinstructions stored in the first memory to cause the shaft to stoprotating when the sensor indicates that the dosing cycle is complete.

The second processor may be configured to execute second programmedinstructions stored in a second memory to communicate data to and fromthe patch pump via the wireless communication chip. The data may beindicative of battery life of a rechargeable battery disposed within thepump housing. Alternatively, the data may be indicative of at least oneof the wearer's heart rate and physiologic parameters. The secondprocessor may configured to execute second programmed instructionsstored in the second memory to calculate when to deliver the doses ofmedication and/or to adjust the calculation based on the data received.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The medication infusion device further may include a pusherconfigured to be coupled to a plunger of the cartridge and a pump motorcoupled to the pusher and configured to move the pusher towards theplunger of the cartridge. The pusher may be configured to deform theplunger of the cartridge to move the medication in the cartridge towardsthe transcutaneous portion to cause a predetermined volume of medicationto be moved out of the cartridge.

The pusher may be coupled to a dosing system comprising a dosing tubeconfigured to receive medication. The dosing tube may have a reservoirsized for generating a predetermined dose of medication with thepredetermined volume selected for delivery to the wearer. The plungermay be flexible and configured to deform when a force is applied. Theplunger may include a first end coupled to the pusher and a second end,opposite the first end and configured to contact the medication withinthe cartridge. The pusher may be configured to cause the first end ofthe plunger to move a first distance relative the transcutaneousportion, when a pressure within the cartridge is a first pressure, todeliver a first dose of medication. The pusher further may be configuredto cause the first end of the plunger to move a second distance relativethe transcutaneous portion, when the pressure within the cartridge is asecond pressure, the second pressure greater than the first pressure, todeliver a second dose of medication. The first distance may be the sameas the second distance.

The pusher may be configured to cause the second end of the plunger tomove a third distance relative the transcutaneous portion, when thepressure within the cartridge is the first pressure, to deliver thefirst dose of medication. The pusher further may be configured to causethe second end of the plunger to move a fourth distance relative thetranscutaneous portion, when the pressure within the cartridge is thesecond pressure, to deliver the second dose of medication. The thirddistance may be greater than the fourth distance. Further, the thirddistance may less than the first distance and the fourth distance may beless than the second distance.

The volume of the first dose of medication and the volume of the seconddose of medication may be the same ±5%. The predetermined volume of thepredetermined dose of medication may be 0.08-1 uL, 0.2-0.6 uL, 0.2 to0.3 uL, or 0.25 uL±5%. The pusher may apply a force on the plunger ofthe cartridge to maintain pressure within the cartridge between 250 mbarto 2000 mbar, between 400 mbar to 1200 mbar, or between 600 mbar to 900mbar.

The pusher may include a screw (e.g., a worm screw), a nut configured tomove along the screw, a bendable rod coupled to the nut, and a cartridgecontactor coupled to the nut and configured to deform the plunger. Thedosing system further may include a plurality of levers configured tocontact the dosing tube to move a predetermined dose of medicationtowards the transcutaneous portion and a circular cam including a shaftoriented in a first plane and a circular plate oriented in a secondplane. The circular plate may be coupled to the shaft and may includesurfaces configured to move the plurality of levers in a series of stepsupon rotation of the shaft. The rotation of the shaft may deliver thepredetermined dose of medication towards the wearer. The shaft may beconfigured to rotate upon rotation of the screw. The plurality of leversmay be configured such that at least one lever is configured to be in alowered position to close a portion of the dosing tube during the entiretime the pump motor moves the pusher.

In accordance with another aspect, a medication infusion device isprovided that includes a patch pump configured to be removably adheredto a wearer's skin for delivering doses of medication (e.g., insulin)from a cartridge (e.g., a pre-filled cartridge) through a transcutaneousportion. The medication infusion device may include a first pumpingsystem including a pusher configured to be coupled to a plunger of thecontainer and a pump motor coupled to the pusher and configured to movethe pusher towards the plunger of the container such that medication ismoved out of the container. The medication infusion device further mayinclude a second pumping system configured to receive the medicationpumped out of the container by the first pumping system, the secondpumping system disposed between the container and the wearer's skin. Thesecond pumping system may include a plurality of levers configured tocontact a dosing tube to move a predetermined dose of the medicationtowards the transcutaneous portion. The plurality of levers may beconfigured such that at least one lever is configured to be in a loweredposition to close the flow between the container and the wearer's skinat all times. The at least one lever may be configured to be in thelowered position at all times to maintain pressure in the container atall times. The second pumping system may be configured to inject avolume of medication that varies slightly around a predetermined volume(e.g., 0.2-0.3 uL) according to its input pressure.

The plunger may be flexible and configured to deform when a force isapplied. The plunger may include a first end coupled to the pusher and asecond end, opposite the first end and configured to contact themedication within the cartridge. The pusher may apply a force on theplunger of the container to maintain pressure within the containerbetween 600 mbar and 900 mbar. The pusher may include a screw, a nutconfigured to move along the screw, a bendable rod coupled to the nut,and a container contactor coupled to the nut and configured to deformthe plunger. Alternatively or additionally, the pusher may include ascrew, a nut configured to move along the screw, a bendable rod coupledto the nut, and a container contactor coupled to the nut and configuredsuch that the pusher incorporates a certain strain.

The second pumping system further may include a dosing tube configuredto receive medication, the dosing tube having a reservoir sized to holdthe predetermined dose of medication for delivery to the wearer. Thesecond pumping system further may include a circular cam having a shaftoriented in a first plane and a circular plate oriented in a secondplane. The circular plate may be coupled to the shaft and may includesurfaces configured to move the plurality of levers in a series of stepsupon rotation of the shaft, wherein rotation of the shaft delivers thepredetermined dose of medication towards the wearer. The shaft may beconfigured to rotate upon rotation of the screw.

In accordance with another aspect, an applicator for use with amedication infusion device is provided. The applicator may be configuredto be removed from the wearer's skin after application and prior todelivery of the doses of medication. The applicator may include anapplicator needle configured to be positioned within a lumen of acannula in a pre-deployment state, a link coupled to the applicatorneedle, an actuator. The actuator may be configured to, upon actuation,cause the link to rotate about an axis to advance the applicator needleand the cannula into the wearer's skin. The actuator further may beconfigured to fully withdraw the applicator needle from the cannula in adeployment state such that at least a portion of the cannula remains inthe wearer's skin. The link may rotate in a single direction to advancethe applicator needle and the cannula into the wearer's skin and tofully withdraw the applicator needle from the cannula.

The applicator may include a biasing member configured to bias the linkto cause the link to rotate about the axis upon actuation. Theapplicator further may include a stopping zone configured to clamp thelink and the applicator needle to reduce the noise of the link and theapplicator needle. The link and the applicator needle may stop rotationwhen the biasing member is fully unloaded. The link and the applicatorneedle may stop rotation without contacting a hard stopping surface. Thelink may include a first interface and the cannula may include a secondinterface configured to contact the first interface and to permitrotational movement during insertion of the cannula into the wearer'sskin.

The applicator further may include a channel comprising at least oneledge. The cannula may include at least one clip disposed at a proximalend. Upon actuation, the at least one clip of the cannula may beconfigured to slide along the at least one ledge of the channel suchthat the cannula moves along a substantially straight path. The actuatormay be configured to, upon actuation, cause the cannula to be insertedbelow the derma layer of the wearer's skin, for example, at an angle of40-50 degrees from the surface of the wearer's skin.

In another embodiment, the applicator for inserting a cannula into awearer's skin may include an applicator needle, a link, and an actuator,as described above, as well as a biasing member coupled to the link. Thebiasing member may be configured to bias the link to cause the link torotate about the axis upon actuation. The biasing member further may beconfigured to transition from a biased position to an unbiased positionupon actuation. In the pre-deployment state, the biasing member may beconfigured to interact with a blocking mechanism such that the biasingmember is fixed in a biased state and, upon actuation, the blockingmechanism may be configured to transition to release the biasing membersuch that the biasing member transitions from the biased state to theunbiased state. The link may configured to rotate in a single directionto advance the applicator needle and the cannula into the wearer's skinand to fully withdraw the applicator needle from the cannula.

The applicator further may include a channel having at least one ledgeand/or at least one guiding arm. The cannula may have at least one clipdisposed at a proximal end and/or at least one wing disposed at theproximal end. Upon actuation, the at least one clip of the cannula isconfigured to slide along the at least one ledge of the channel suchthat the cannula moves along a substantially straight path and the atleast one wing of the cannula is configured to slide along the at leastone guiding arm in order to minimize rotation of the cannula around thelongitudinal axis of the cannula

A method for inserting a cannula for delivering doses of medication to awearer's skin is also provided, the method including selecting anapplicator including an applicator needle, a link, and an actuator, asdescribed above, and actuating the actuator to cause the applicator torotate the link about an axis, advance the applicator needle and thecannula into the wearer's skin, and withdraw the applicator needle fromthe cannula in a deployment state. Actuating the actuator further maycause the applicator to transition a biasing member, as described above,from a biased state to an unbiased state, which may cause rotation ofthe link and then withdrawal of the applicator needle from the cannula.The applicator further may include at least one stopping zone configuredto slow the rotation of the link about the axis, for example, duringwithdrawal of the applicator needle from the cannula.

In the pre-deployment state, the biasing member may be configured tointeract with a blocking mechanism such that the biasing member is fixedin a biased state. Actuating the actuator further may cause theapplicator to transition the blocking mechanism to a position whereinthe biasing member does not interact with the blocking mechanism suchthat the biasing member transitions from the biased state to theunbiased state.

Advancing the applicator needle and the cannula into the wearer's skinmay include advancing the applicator needle and the cannula along achannel having at least one ledge. The cannula may have at least oneclip disposed at a proximal end and configured to slide along the atleast one ledge of the channel such that the cannula moves along asubstantially straight path. The channel further may include at leastone guiding arm and the cannula may have at least one wing disposed atthe proximal end such that advancing the applicator needle and thecannula into the wearer's skin includes sliding the wings along the atleast one guiding arm in order to minimize rotation of the cannulaaround the longitudinal axis of the cannula.

In accordance with another aspect, a system for use with a medicationinfusion device is provided. The system may include a pad configured tobe adhered to the wearer's skin and an applicator configured to belocked to the pad during placement of the pad on the wearer's skin. Theapplicator may include a housing configured to house a cannulatherewithin during a pre-deployment state and an actuator. The actuatormay be configured to, upon actuation, cause the cannula to be advancedto lock the cannula to the pad and unlock the applicator from the padsuch that at least a portion of the cannula is advanced into thewearer's skin in a deployment state wherein the pad remains adhered tothe wearer's skin and the applicator, once unlocked, is removable fromthe pad.

The applicator further may include at least one attachment pad couplerconfigured to lock the applicator to the pad in a pre-deployment state.The cannula may include at least one clip disposed at a proximal end andconfigured to lock the cannula to the pad in a deployment state. Theactuator may be configured to, upon actuation, cause the at least oneclip of the cannula to be advanced such that the at least one attachmentpad coupler of the applicator is moved to unlock the applicator from thepad.

In accordance with another aspect, a cannula for use with a medicationinfusion device is provided. The cannula may include an elongated shaft,a tip, and a cannula head. The elongated shaft may have a lumenextending therethrough and one or more apertures for medicationinfusion. The one or more apertures may include a proximal apertureoriented away from a skin surface of the wearer. The elongated shaft mayhave a conical shape configured to limit kinking during deployment ofthe cannula. The tip may be disposed at a distal end of the elongatedshaft and may be configured to be inserted into the wearer's skin. Thetip may be cut with an angle and oriented to avoid unintentionalpiercing of a wall of an applicator.

The cannula head may be disposed at a proximal end of the elongatedshaft and may include one or more clips oriented relative to the one ormore apertures to axially orient the one or more apertures relative to atarget infusion area within the wearer. The one or more clips mayinclude one or more protrusions configured to protrude outwardly fromthe cannula head. The cannula head further may include one or more wingsthat protrude towards the wearer's skin. The wings may be configured tofurther axially orient the one or more apertures relative to the targetinfusion area within the wearer. The cannula head further may includeone or more interfaces to couple with an applicator during deployment ofthe cannula. The one or more interfaces may permit rotational movementduring deployment of the cannula and may include first and secondrounded interfaces. The first rounded interface may be convex and thesecond rounded interface may be concave.

The elongated shaft, the tip, and the cannula head may be integrallyformed from a single piece of material. For example, the cannula may beinjection molded from a single piece of material. The cannula furthermay include self-sealing septum disposed within the cannula head and oneor more knife blades at the tip configured to extend outwardly from theelongated shaft.

A method for deploying a transcutaneous device for use with a medicationinfusion device for delivering doses of medication is also provided, themethod including providing a cannula including an elongated shaft, atip, and a cannula head having clips, as described above, inserting thetip into a wearer's skin, and guiding the one or more clips duringcannula insertion such that the one or more apertures are axiallyoriented relative to a target infusion area within the wearer when thecannula is transcutaneously deployed. The method further may includedelivering doses of the medication transcutaneously into the lumen ofthe cannula and out the one or more apertures to the target infusionarea.

After inserting the tip into the wearer's skin, the cannula may becoupled to an adhesive pad. Coupling the cannula to the adhesive pad mayinclude inserting the one or more clips into one or more pad attachmentsdisposed on the adhesive pad. The cannula head further may include oneor more wings that protrude towards the wearer's skin. Coupling thecannula to the adhesive pad further may include inserting the one ormore wings between two pad attachments of the one or more padattachments such that rotation of the cannula is reduced. To furtherreduce rotation of the cannula, the tip of the cannula may include oneor more knife blades that extend outwardly from the elongated shaft.

In accordance with another aspect, a system for orienting a cannula isprovided. The system may include a cannula for use with a medicationinfusion device configured to be removably adhered to a wearer's skinfor delivering doses of medication transcutaneously and an adhesive padconfigured to be removably adhered to the wearer's skin. The cannula mayinclude an elongated shaft, a tip, and a cannula head, as describedabove. The cannula may be configured to couple to the adhesive pad,which may have one or more pad attachments. One or more clips of thecannula may be sized and shaped to fit within the one or more padattachments.

The cannula may be configured such that the cannula is oriented aparticular way upon insertion, for example, such that a proximalaperture of the one or more apertures of the cannula is oriented awayfrom a skin surface of the wearer. The tip of the cannula may be cutwith an angle and oriented to avoid unintentional piercing of a wall ofan applicator. Further, the cannula head may include one or more wingsthat protrude towards the wearer's skin. The wings may be sized andshaped to fit between two pad attachments of the one or more padattachments and may be configured to further axially orient the one ormore apertures relative to the target infusion area within the wearer.

In accordance with another aspect, a cannula for use with a medicationinfusion device is provided. The cannula may include an elongated shafthaving a lumen extending therethrough and one or more apertures formedication infusion and a tip at a distal end of the elongated shaftconfigured to be inserted into the wearer's skin. The cannula furthermay include a biodegradable material disposed in or adjacent to at leastone of the one or more apertures to block delivery of medicationtherethrough in an initial state. The biodegradable material may beconfigured to biodegrade within the wearer over a period of time (e.g.,2-3 days or 4-6 days) to unblock the at least one aperture to permitdelivery of medication therethrough. The use of biodegradable materialsexpands the insulin infusion area and volume over time.

At least one of the one or more apertures may be unblocked in theinitial state to permit delivery of medication therethrough. The atleast one aperture unblocked in the initial state may be a distal-mostaperture. Alternatively, the at least one aperture unblocked in theinitial state may be a proximal-most aperture.

The cannula further may include a second biodegradable material disposedat least one of the one or more apertures to block delivery ofmedication therethrough in a second state, the second biodegradablematerial configured to biodegrade within the wearer over a second periodof time, different from the period of time, to unblock the at least oneaperture to permit delivery of medication therethrough. The one or moreapertures may include a proximal aperture and a distal aperture. Thebiodegradable material may be disposed in or adjacent to the proximalaperture and the second biodegradable material may be disposed in oradjacent to the distal aperture such that the proximal aperture and thedistal aperture are unblocked at different times. The period of time maybe 2-3 days and the second period of time may be 4-6 days.

The cannula further may include a tip aperture disposed at the tip ofthe cannula. The biodegradable material may be disposed within the lumensuch that the tip aperture is blocked. Alternatively, the biodegradablematerial may be disposed within the one or more apertures such that thetip aperture is unblocked.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features, aspects, and advantages of the presentinvention will become apparent from the following description, appendedclaims, and the accompanying exemplary embodiments shown in thedrawings, which are briefly described below.

FIG. 1 illustrates an exemplary medication infusion system having apatch pump for delivering medication in accordance with the principlesof the present invention.

FIG. 2 is a diagram showing exemplary attachment zones for the patchpump and an external sensor such as a continuous glucose monitoringsensor.

FIGS. 3A and 3B are, respectively, perspective and exploded views of anexemplary pad and applicator for attaching a pad and inserting acannula.

FIGS. 4A and 4B are cross-sectional perspective and side views of theapplicator and pad.

FIG. 5A is a perspective view of exemplary internal components of theapplicator of FIG. 4 in a pre-assembled state and FIG. 5B is aperspective view of the internal components of the applicator in anassembled state.

FIG. 6 is a perspective view of the internal components and mechanismfor inserting the cannula.

FIGS. 7A-7D are plan views of the mechanism and steps for inserting thecannula.

FIG. 8 is a cross-sectional side view of a lower stopping portion of theapplicator showing needle retraction.

FIGS. 9A and 9B are perspective views of an exemplary pad for attachingthe pump to a wearer.

FIGS. 10A and 10B are plan views of the applicator and pad duringinsertion of the cannula.

FIG. 10C is a cross-sectional perspective view of the cannula andapplicator during insertion of the cannula

FIGS. 10D-10F are plan, perspective, and side views of the cannulacoupled to the pad after the applicator is removed.

FIG. 11A is a cross-sectional side view of the applicator, pad, andcannula showing the cannula inserted into the wearer.

FIG. 11B is a cross-sectional side view of the pad, cannula, andassembled pump showing how the microdosing tubing couples to the cannulato deliver microdoses of medication transcutaneously.

FIGS. 12A and 12B are perspective views of an exemplary cannula fordelivering medication.

FIGS. 13A and 13B are perspective views of alternative embodiments ofthe distal end of the cannula.

FIG. 14A is a cross-sectional side view of the cannula and multipleexemplary apertures.

FIGS. 14B-14E are cross-sectional side views of alternative embodimentsof the cannula comprising biodegradable materials.

FIGS. 15A and 15B are perspective views of an exemplary patch pump witha pump-cap assembly.

FIG. 16 is a perspective view of the skin-facing side of the pump-capassembly.

FIG. 17 is an exploded view of the pump.

FIG. 18 is a perspective view of the skin-facing side of the patch pump,with a portion of the pump housing and the cap housing removed.

FIGS. 19A and 19B are plan views of the upper and lower sides of anexemplary circuit board disposed within the pump.

FIG. 20A is a cross-sectional plan view of the patch pump when thecartridge is full.

FIG. 20B is a cross-sectional plan view of the patch pump when thecartridge is empty.

FIG. 20C is a cross-section plan view of the wet and dry zones withinthe patch pump.

FIG. 21A is a perspective view of exemplary internal components of thepatch pump.

FIGS. 21B and 21C are, respectively, perspective and plan views of theinternal components of the patch pump, with certain electricalcomponents removed.

FIG. 22A is a cross-sectional perspective view of an exemplary contactsensor disposed within the pump.

FIGS. 22B and 22C are, respectively, cross-sectional side views of thecontact sensor in a contacting and non-contacting position.

FIG. 23A is a perspective view of an exemplary gearbox within the pump.

FIG. 23B is a cross-sectional side view of an exemplary pressure sensordisposed within the pump.

FIG. 24A is a graph showing the relationship between pressure and volumeof medication within the cartridge and microdosing unit.

FIGS. 24B and 24C, are, respectively, graphs showing the relationshipbetween the number of dosing cycles and the amount of medicationdelivered per cycle, without and with initialization.

FIG. 24D is a graph showing the accuracy of the pump with and withoutthe microdosing system.

FIG. 24E is a graph showing a comparison of the percentage error of flowfor the patch pump and other commercially available pumps.

FIG. 24F is a schematic depiction of an exemplary pusher and microdosingsystem.

FIG. 25A is an exploded view of an exemplary cap.

FIG. 25B is a side view of an exemplary microdosing system disposedwithin the cap, wherein an exemplary circular cam is in aninitialization position.

FIG. 25C-25F are side views of the microdosing system wherein thecircular cam is in a non-gripping position, a gripping position, asliding position, and a dosing position.

FIGS. 26A and 26B are, respectively, perspective views of exemplarydampers and mating surfaces.

FIGS. 27A and 27B are perspective views of an exemplary microdosingsystem that may be incorporated in the cap.

FIG. 27C is a perspective view of the microdosing system, wherein anexemplary lever system is spaced apart from the tube of the microdosingsystem.

FIG. 27D is a cross-sectional side view of the microdosing system withthe lever system in an assembled position.

FIGS. 28A and 28B are, respectively, perspective views of an exemplarycircular cam and lever system that may be used in the microdosingsystem.

FIGS. 29A-29C are, respectively, cross-sectional perspective andcross-sectional side views of the lever system and exemplary dosingtube.

FIG. 29D is a perspective view of the microdosing system, wherein theexemplary lever system and lever springs are removed.

FIGS. 30A, 30C, 30E, 30G, 30I, and 30K are side views of the microdosing system over an exemplary series of steps configured to deliver apredetermined dose of medication to the wearer.

FIGS. 30B, 30D, 30F, 30H, 30J, and 30L are cross-sectional side views ofthe microdosing system over the series of steps configured to deliverthe predetermined dose of medication to the wearer.

FIG. 31 is a schematic depiction of the series of steps configured todeliver the predetermined dose of medication to the wearer.

FIGS. 32A and 32B are, respectively, schematic depictions of anexemplary system configured to detect an occlusion in the dosingpathway.

FIG. 32C is a schematic depiction of the position of a lever of themicrodosing system during a dosing cycle, wherein the dosing pathway isnot occluded.

FIGS. 33A and 33B are, respectively, schematic depictions of the seriesof steps configured to deliver the predetermined dose of medication tothe wearer, wherein the dosing pathway is not occluded and wherein thedosing pathway is occluded.

FIGS. 33C and 33D are, respectively, schematic depictions of theposition of a lever of the microdosing system during a dosing cycle,wherein the dosing pathway is not occluded and wherein the dosingpathway is occluded.

FIG. 34 is a graph showing hall-effect sensor values over time when thedosing pathway is not occluded and when the dosing pathway is occluded.

FIGS. 35A-35D are plan views of the circular cam and an exemplary systemconfigured to determine the position of the circular cam.

FIG. 35E is a graph showing signal strength over time as the circularcam rotates.

FIGS. 36A and 36B are, respectively perspective views of an exemplarytube flatting system before and after the dosing tube is flattened.

FIG. 37 is a perspective view of an exemplary welded dosing tube used inthe microdosing system for precise medication dosing.

FIG. 38A is a cross-sectional side view of the pump-cap assembly whenthe pump and cap are locked together.

FIG. 38B is a cross-sectional side view of the pump-cap assembly whenthe pump-cap assembly and pad are locked together.

FIG. 38C is a cross-sectional side view of a distortion that may occurif the pump-cap assembly and pad are not locked together.

FIGS. 39A and 39B are, respectively, perspective and cross-sectionalside views of the pump-cap assembly in an open, unlocked position.

FIGS. 39C and 39D are, respectively, cross-sectional side views of thepump-cap assembly in closed, unlocked and locked positions.

FIGS. 39E and 39F are, respectively, perspective views of the pump-capassembly in open, unlocked, and locked positions.

FIG. 40A is a perspective view of exemplary locking protrusions disposedon the cap.

FIG. 40B is a perspective view of exemplary locking receptacles on thepump.

FIG. 41 is a perspective view of an exemplary cartridge that may be usedand replaced in the system described herein.

FIG. 42 is a perspective view of the charging system for charging thebattery in the reusable pump.

FIG. 43A-43G are screenshots of an exemplary software application thatmay be used in the systems described herein.

DETAILED DESCRIPTION

Provided herein are systems and methods for delivering fluid to apatient. For example, medication such as insulin may be deliveredtranscutaneously using patch pumps that are user-friendly,environmentally-friendly, lower cost, discreet, less prone to errors,and/or that provide precise, repeatable doses of medication. As anotherexample, the patch pump may incorporate components for rapid occlusiondetection. Accessories for applying the patch pump to the patient's skinand managing the patch pump also are provided. In a preferredembodiment, the system includes a wearable insulin pump having apatch-style form factor for adhesion to a user's body surface.

The systems and methods described herein may be used to delivermedication including, but are not limited to, insulin, antibiotics,nutritional fluids, total parenteral nutrition or TPN, analgesics,morphine, hormones or hormonal drugs, gene therapy drugs,anticoagulants, analgesics, cardiovascular medications, AZT orchemotherapeutics. The types of medical conditions that the systems andmethods might be used to treat include diabetes, cardiovascular disease,pain, chronic pain, cancer, ADDS, neurological diseases, Alzheimer'sDisease, ALS, Hepatitis, Parkinson's Disease or spasticity. Preferably,the systems and methods are optimized for transcutaneous delivery ofinsulin to users with diabetes including Type I Diabetes Mellituspatients.

Referring to FIG. 1 , an exemplary medication infusion system includinga patch pump for delivering medication is described. In FIG. 1 ,components of the system are not depicted to scale on either a relativeor absolute basis. Medication infusion system 10 may include applicator100, cannula 200, pump 300, cap 400, cartridge 500, charging system 600,and/or software application 700. Preferably, applicator 100, cannula200, cap 400, and cartridge 500 are disposable components that may bereplaced approximately every 3-10 days and/or once the pre-filledcartridge is empty, while pump 300 is reusable and may last for anextended period of time, e.g., approximately 2-4 years. As such, pump300 may be used with many different applicators, cannulas, caps, andpre-filled cartridges. Such a configuration is expected to promotesanitary use of the system, as the components exposed to the patient andthe insulin are disposable, while reducing costs for componentscontaining more expensive electronics, e.g., pump 300, charging system600, and/or software application 700, which may be used repeatedly. In apreferred embodiment, system 10 includes a second pump, such that thewearer may charge the second pump while using the first pump and viceversa. In this manner, the wearer will always have a pump that ischarged and ready to be used once the cartridge of the pump in use isempty. Further, this system is designed to reduce waste while reducingthe number of times the wearer is required to insert a new cannula.Medication infusion system 10 may be used to apply cannula 200 and a padto a wearer and to deliver medication through cannula 200 via a patchpump coupled to the pad.

Applicator 100 is configured to apply an adhesive pad to the wearer and,upon actuation, to insert cannula 200 into the wearer. The pad isconfigured to be secured to the wearer for a period of time, e.g., atleast 3 days, 7-10 days, and then may be replaced by a similar pad usinga similar applicator. The pad may include a pad skeleton having one ormore locking mechanisms that are configured to couple the pad toapplicator 100 for insertion of cannula 200 or to the assembled pump fordelivery of medication. Applicator 100 may include an internal componentconfigured to support an insertion mechanism designed to insert cannula200 through the skin of the wearer via rotational movement and to guideand orient cannula 200 during insertion.

Preferably, applicator 100 is designed to suppress noise duringinsertion. The insertion mechanism may include an applicator needleconfigured to pierce the wearer's skin and a biasing member, which maybe coupled to one or more links configured to interact with cannula 200and the applicator needle. Upon actuation by the wearer, the insertionmechanism preferably rotates and applies a distal force on cannula 200and the applicator needle within cannula 200, such that cannula 200 isinserted through the wearer's skin. Cannula 200 may include a proximalcannula head configured to couple to one or more locking mechanisms onthe pad skeleton and, at the same time, uncouple applicator 100 from thepad skeleton. The insertion mechanism further may be configured tocontinue rotating to withdraw the applicator needle from cannula 200 andto store the applicator needle within the applicator after cannula 200is inserted.

Cannula 200 is designed to receive medication doses from a patch pumpand to deliver the medication through one or more apertures. The one ormore apertures may be disposed at the distal tip and/or along theelongated shaft of cannula 200 such that the medication is deliveredalong the length of elongated shaft. Preferably, the apertures arearranged and oriented such that the medication is delivered only belowthe derma layer of skin. Cannula 200 may include a cannula head having aself-sealing septum configured to support and guide the applicatorneedle during insertion of cannula 200 and the outflow needle of cap 400during delivery of medication. In some embodiments, cannula 200 may bedesigned to change the location at which medication is delivered to thepatient via the aperture(s) over time without repositioning cannula 200in the patient's skin. Such a design is expected to extend the life ofcannula 200 within the patient, allowing transcutaneous implantation foraround 10 days or more. Further, such design may reduce the risk ofcannula occlusion. In some embodiments, cannula 200 may include one ormore biodegradable materials disposed within the lumen and/or theapertures of cannula 200 that are configured to dissolve over a periodof several days, thereby opening new apertures over time through whichmedication is delivered via the cannula.

Pump 300 is designed to pump medication from cartridge 500 through themicrodosing system, through a transcutaneous portion, and into thewearer. The transcutaneous portion preferably includes a cannulainserted into the wearer's skin, the cannula configured to befluidically coupled to a needle and having one or more apertures beneaththe outer skin layer for delivery of the dose of medication. Pump 300 isdesigned to be removably coupled to cap 400 and the pad to form a patchpump, which is configured to deliver doses of medication through cannula200 transcutaneously to the patient. The pump-cap assemblyadvantageously provides precise, repeatable microdoses of medication tothe wearer. Pump 300 preferably is designed to be used for an extendedperiod of time, e.g., over 1 year and more preferably up to 2-4 years,and may be manufactured to include a minimal number of parts. Forexample, in order to lower the cost of the patch pump, pump 300 mayinclude less than 15 parts. After a cartridge of medication is used, abattery within pump 300 is charged and, after charging, the cartridgeand cap may be removed and discarded, leaving pump 300 ready to be usedagain with a new cartridge and a new cap. Pump 300 may include a motordisposed within the pump housing and may be configured to move a pushertowards a plunger of cartridge 500 such that insulin is advanced throughan inflow needle of cap 400 and to a microdosing system designed tomeasure and deliver predetermined doses of medication.

Pump 300 preferably includes a controller disposed within the pumphousing for controlling operation of pump 300. For example, thecontroller may store instructions that, when executed, cause pump 300 toperform the operations described herein. In some embodiments, thecontroller of pump 300 may include a two processor architecture to, forexample, to enhance the security of the pump. The first processor maycontrol pumping while the second processor communicates data to and fromthe pump via a wireless chip.

Advantageously, the first and second processors may be operativelyde-coupled such that communication of data from outside the pump,handled by the second processor, does not interfere with thepump-related workings executed by the first processor. By isolating thepump processing from the external communication processing, security ofthe pump is enhanced.

Pump 300 further may include one or more sensors designed to senseinformation associated with operation of pump 300 and/or physiologicalinformation associated with the wearer. The controller receivesinformation from the sensor(s) and may adjust the algorithms associatedwith the pump based on such information. Additionally or alternatively,the controller may cause an alert based on the information from thesensor(s) to be issued. In some embodiments, pump 300 includes one ormore skin sensors that detect skin of the wearer. The controller maycause the pump motor to activate only if a skin sensor on theskin-facing side of the pump housing detects skin. Pump 300 further mayinclude a locking mechanism to lock pump 300 to cap 400 and thecontroller further may only unlock the pump after pump 300 reaches apredetermined state (e.g., the battery is charged and/or the pusher isreset to a home position). The controller further may monitor one ormore sensors disposed within, on, or separate from the pump housing andalert the wearer via a vibration motor, an LED(s) of a user interface ofthe pump housing, a sound generator, or a mobile application based onthe information sensed by the sensors.

The sensors may include a contact sensor configured to detect a positionof pumping components within the pump housing, a sensor configured tomonitor the function of cap 400, (e.g., to detect an occlusion in thedosing pathway, such as within the microdosing system of cap 400 orwithin the cannula), a position sensor configured to detect a positionof a cam plate within the microdosing system of cap 400, a pressuresensor configured to detect the pressure within cartridge 500, aphotoplethysmography sensor configured to detect a wearer's heart rateor other physiologic parameters, an accelerometer, a temperature sensor,a pressure sensor, a humidity sensor, an optical sensor to detect theinsulin concentration in the cartridge via a specific marking on thecartridge that indicates the insulin concentration, and/or a continuousglucose monitoring sensor.

Cap 400 preferably receives medication from cartridge 500 moved intotubing of cap 400 as a result of pumping by pump 300. Further, cap 400may deliver predetermined doses of the medication through an outflowneedle, into cannula 200, and to the wearer. Cap 400 preferably isdesigned to be replaced after the cartridge is empty or when thetemperature sensor detects a temperature exceeding a predeterminedtemperature threshold, the temperature indicating that the insulin wasdamaged due to long exposure at a high temperature. Preferably, cap 400is also manufactured to include a minimal number of parts, such as 15parts, in order to lower the cost of cap 400. Cap 400 may include amicrodosing system configured to measure and deliver the predetermineddoses of medication. The microdosing system may be configured to onlydeliver the predetermined dose of medication upon initialization of themicrodosing system, for example, once the controller determines, basedon information from the sensor, that the pressure within cartridge 500is within a predetermined range. The microdosing system may include adosing tube having a flattened portion configured to hold thepredetermined dose, a cam plate coupled to a cam shaft, the cam platehaving one or more raised surfaces, and/or a lever system configured totransition between a raised position and a lowered position upon contactwith the raised surfaces of the cam plate when the cam shaft is rotated.Cap 400 further may include locking mechanisms configured to lock cap400 to pump 300 and/or to the pad skeleton.

Cartridge 500 is an enclosed container designed to hold the medicationfor infusion into the patient. Cartridge 500 may be a commerciallyavailable insulin container such as the NovoRapid PumpCart availablefrom Novo Nordisk A/S of Bagsværd, Denmark. Cartridge 500 preferably ispre-filled with a plurality of doses of medication such as insulin. Thepatch pump is designed such that when cartridge 500 is inserted into thepump patch, the cartridge 500 is completely encased by pump 300 and cap400. Cartridge 500 may include a cartridge cap through which is disposedan inflow needle of cap 400. Cartridge 500 further may include aflexible plunger configured to be advanced towards the cartridge cap,responsive to pumping by pump 300. As the plunger is displaced, insulinis delivered to a microdosing system of cap 400, which in turn deliverspredetermined doses of medication to the wearer one at a time. Oncecartridge 500 is empty, it may be replaced by a similar pre-filledcartridge.

Charging system 600 is configured to charge one or more batteries withinpump 300, e.g., via respective inductive coils disposed within thehousing of a charger and pump 300. The charger is delivered with a USB-Cto USB-A cable. The cable may be plugged into a standard USB-A socket(e.g. on an adapter put into a conventional wall electrical socket, on acomputer, or in public transport), for charging components within thecharger to permit charging pump 300.

Software application 700 is designed to cause a computer (e.g.,smartphone, laptop, desktop, tablet, smartwatch, etc.) to communicatedata with pump 300 and display information on the pump to a wearer in auser-friendly manner. Software application 700 may cause the computer tosecurely exchange data between two or more pumps that are used by asingle wearer. Software application 700 preferably receives data fromthe second processor of pump 300 and may cause the computer to transmitsuch data to a second pump while pump 300 is charging. Softwareapplication 700 further may cause the computer to transmit to the patchpumps data indicative of the wearer's activity level and this data maybe used to modify how the wearer is alerted and/or when the doses ofmedication are delivered.

Referring now to FIG. 2 , exemplary attachment zones for the patch pumpand an optional external sensor, such as a continuous glucose monitoringsensor are illustrated. Attachment zones 12 illustrate several locationson the wearer's body where the applicator may attach the adhesive padand insert the cannula and to which the patch pump is secured. Forexample, the patch pump may be secured to the upper arms, abdomen, orthighs of the wearer. As will also be understood by one of ordinaryskill in the art, the patch pump may be secured to other locations onthe wearer.

The patch pump also may be operatively coupled to an optional continuousglucose monitoring sensor, which may transmit data to a controller ofthe patch pump, which data may be used to adjust the time of insulindelivery or the amount of each dose. Preferably, the patch pump receivesdata from continuous glucose monitoring sensor 14, which is configuredto be attached within attachment zones 12. Exemplary continuous glucosemonitors include sensors commercially available from DexCom, Abbott,Eversense, Indigo, or Biolinq.

The sensed glucose levels may be used to adjust the dosing cycles. Forexample, the patch pump may include an algorithm configured to determinewhen to deliver insulin to the wearer. The algorithm may recalculate thetime of delivery depending upon the sensed glucose level such that thewearer's glucose level remains within a safe range. For example, if thewearer's glucose levels fall below a predetermined threshold, thecontroller may cause the patch pump to stop delivering insulin for aperiod of time. Or, if the wearer's glucose levels rise above a certainlevel, the controller may cause the patch pump to deliver a microdose ofinsulin. In addition, responsive to the sensed glucose levels, thealgorithm may adjust the amount of insulin in the dose. For example, astandard dose of insulin may include the amount of insulin deliveredover eight dosing cycles. If the wearer's glucose levels fall below apredetermined threshold, the controller may cause the patch pump todeliver a smaller dose of insulin than the standard dose, for example bypermitting only 4 dosing cycles or 0 dosing cycles (stopping the pump).

Further, as described above, software application 700 may receiveinformation from the continuous glucose monitoring sensor or othermonitoring systems, for example, sensed glucose levels, informationabout patient food intake, and/or information about patient's activitylevels (e.g., due to exercising, playing sports). This information maybe transferred to the patch pump via the communication circuitry and theprocessor of the pump and the patch pump may respond to the transferredinformation, causing the patch pump to adjust the timing and/or amountof each dose. In this manner, the pump is modular and interchangeablewith many continuous glucose monitoring sensors or other monitoringsystems, making the pump “universal.” Advantageously, the patch pumpdescribed herein may be used with a minimal amount of externalmonitoring while still being effective at delivering accurate microdosesof medication at levels to treat the wearer. The inclusion of sensorswithin the patch pump, such as the PPG sensor and a sensor fordetermining activity level, may result in less external monitoringsystems, which can be beneficial for the wearer. For example, in oneembodiment, the patch pump may only be used with a commerciallyavailable CGM sensor.

Applicator, Pad, and Method for Inserting Cannula

Referring now to FIGS. 3A and 3B, perspective and exploded views of anexemplary pad and applicator are described. Applicator 100 maytranscutaneously apply a cannula, upon actuation by a user, which isdesigned to deliver doses of medication (e.g., insulin) from a patchpump configured to be removably coupled to the cannula. Advantageously,applicator 100 further may apply a pad that is adhered to the wearer'sskin and then coupled to the patch pump. For example, actuation ofapplicator 100 may both insert the cannula and cause the cannula to belocked to the adhesive pad in a single actuation. Further, applicator100 may include internal components designed to minimize noise duringthe actuation process. For example, applicator 100 may avoid clicksand/or hard stops that make audible noises during insertion of thecannula.

In a pre-actuation state, applicator 100 may be coupled to pad 102 asshown in FIG. 3A. For example, applicator 100 may be coupled to pad 102via pad skeleton 104 of pad, which is disposed on a first surface of pad102. Skin-safe pad adhesive 105 may be disposed on a second, skin-facingsurface of pad 102 such that the pump-pad assembly may be attached to awearer for a period of time, for example, 3-5 days, 3-10 days, or 10days or more. One or more release liners 103 may be attached to padadhesive 105 until pad 102 is ready to be secured to the wearer. Padskeleton 104 may be a frame with a shape designed to surround thepump-cap assembly so as to securely couple the adhesive pad to thepump-cap for wearing by the patient. Pad skeleton 104 may be designed toremovably couple portions of pad 102 to applicator 100 in thepre-actuation state. For example, pad skeleton 104 may have one or moreattachment mechanisms to lock pad 102 to applicator 100 and unlock uponactuation of applicator 100. Advantageously, the attachment mechanismsalso may lock the cannula to pad 102 after actuation. As depicted inFIG. 3A, pad skeleton 104 may have pad attachments 106 at a first end ofpad 102 and pad back clip 108 at a second end of pad 102. Padattachments 106 and pad back clip 108 may interact with applicator 100or a patch pump to lock the pad to applicator 100 or the patch pump. Padattachments 106 may include at least two arms that protrude upwards fromthe pad and away from the skin surface of the wearer. Each arm may havean opening (e.g., slot) to receive extensions from the applicator duringpre-actuation and extensions from the cannula post-actuation. Thus, thearms, which may have a U-shape, and openings may be used to lock to boththe applicator and the cannula. Pad skeleton 104 may also include padclips holes 107 disposed on the sides of pad skeleton 104. Pad clipsholes 107 may be a hole or receptacle sized and shaped to interact witha corresponding feature of the pump-cap assembly such that the pump-capassembly may be locked to the pad. Further, pad 102 may include padopening 109 to allow direct sensing of the wearer's skin by one or moresensors of the pump. For example, the skin sensor(s) and/or the PPGsensor(s) may be positioned at pad opening 109 when the pump is coupledto the pad.

Applicator 100 may include applicator housing 110 and actuator 112.Applicator housing 110 is configured to house the mechanisms forinserting the cannula. After insertion of the cannula, internalcomponent 114 is designed to withdraw and safely store the needle usedto pierce the wearer's skin. Actuator 112, upon actuation, causes thecannula to be transcutaneously inserted into the wearer's skin.Actuation of actuator 112 also may unlock applicator 100 from pad 102.Actuation of actuator 112 also may lock the transcutaneously insertedcannula into pad 102. For example, actuation of applicator 100 mayinsert the cannula transcutaneously, unlock the applicator from the pad,and lock the cannula to the pad in a single actuation. Actuator 112 mayrelease the internal mechanism disposed within applicator housing 110when actuated by the wearer, thus causing the cannula to advance throughthe wearer's skin. Actuator 112 may be a button configured to be pressedby the wearer as illustrated, or may be a lever, snap, knob, or thelike. The mechanism for inserting the cannula may include internalcomponent 114, biasing member 116, and links 118 and 120, which aredisposed within applicator housing 110, and are configured to advancecannula 200 through pad 102 and into the wearer's skin. The mechanismmay further include applicator needle 150, which is configured to bedisposed within cannula 200 during insertion and withdrawn from cannula200 after insertion. Self-sealing septum 224 may be disposed within thecannula head of cannula 200 in order to support and guide applicatorneedle 150 and minimize backflow out of cannula 200.

Referring now to FIGS. 4A and 4B, cross-sectional perspective and sideviews of the applicator and pad are described. Applicator 100 mayinclude one or more attachment mechanisms that are configured tointeract with corresponding features of pad skeleton 104 to lockapplicator 100 to pad 102. These locking mechanisms may help retainapplicator 100 locked to pad 102 when cannula 200 is inserted into theskin of the wearer. For example, applicator 100 may include one or moreback pad couplers 122, which may be coupled to pad back clip 108 at thesecond end of pad 102. Back pad couplers 122 may be extensions thatextend out from the applicator housing to couple with the pad skeleton.As described further below, applicator 100 also may be coupled to pad102 via pad attachments 106 and may be uncoupled from pad 102 at thesame time that cannula 200 is fully inserted into the wearer and lockedto pad 102.

Internal component 114 supports the insertion mechanisms for insertingthe cannula and, after insertion, withdrawing the needle disposed withinthe cannula. Internal component 114 may be coupled to applicator housing110 at an angle. Preferably, internal component 114 is disposed at theangle (e.g., 30-60° angle, 40-50° angle, 45° angle) such that cannula200 is inserted into the skin of the wearer at the same angle. Internalcomponent 114 may be configured to position the tip of cannula 200 nearpad 102, between pad attachments 106, in a pre-deployed state, as shownin FIG. 4B. The insertion mechanisms supported by internal component mayinclude biasing member 116 and links 118 and 120. Biasing member 116 maybe disposed at the proximal end of internal component 114 and preferablyis a spring that may be coupled to one or more links that interact withcannula 200. For example, as described further with respect to FIGS.7A-7D, biasing member 116 may be coupled to link 118, link 118 may becoupled to link 120, and link 120 may be coupled to cannula 200.

Actuator 112 may be disposed above internal component 114, such that,when actuator 112 is pressed towards the skin by the wearer, a forcealso is applied to internal component 114. Actuator 112 may include oneor more activation ribs 113, which are configured to engage withcorresponding protrusions 115 disposed on the top of a lower portion ofinternal component 114. Activation ribs 113 preferably are curved suchthat when a force is applied to actuator 112 by the wearer, the forceapplied to internal component 114 is perpendicular to the angle at whichinternal component 114 is disposed within applicator housing 110.Activation ribs 113 reorient the force to be perpendicular to theinternal component, such that friction is reduced, providing smootherinsertion of the cannula without a stick-slip effect. Activation ribs113 also allow a longer stroke upon activation, which results in morereliable insertion of the cannula.

Referring now to FIGS. 5A and 5B, the internal components of theapplicator are described. Internal component 114 may be injection moldedto form a single piece of material and may be configured to fold inhalf, as depicted in FIG. 5B, such that the internal component is sizedand shaped to fit within the applicator housing. Internal component 114may include upper portion 132 and lower portion 134 connected via hinge136. This configuration reduces the number of parts of the applicator,which contributes to a reduction in costs.

Internal component 114 preferably includes a channel and one or moreguiding mechanisms that are configured to help guide the cannula duringinsertion. An accurate location of insertion helps ensure that insulinis only delivered below the dermal layer of the wearer's skin. Upperportion 132 may include an upper portion of channel 126 and lowerportion 134 may include a corresponding lower portion of channel 126such that, when upper portion 132 is folded on top of lower portion 134,the upper and lower portions of channel 126 form a complete channel.Channel 126 preferably is sized and shaped such that the cannula canmove through the channel toward the wearer's skin. To ensure accuratecontrol of the cannula as it moves through channel 126, additionalguiding mechanisms may guide the cannula on its insertion path. Forexample, the lower portion of channel 126 further may include one ormore ledges 128 configured to interact with corresponding features ofthe cannula when the cannula is advanced in a distal direction.Advantageously, such ledges 128 ensure that cannula is inserted into thewearer's skin at a particular orientation, which may be helpful foraligning radially spaced apertures in the cannula within the wearer'sskin. Further, the guiding mechanisms may extend into channel 126 tocontact and guide cannula on the insertion path during insertion. Forexample, the cannula further may be guided by guiding arm 140 disposedon upper portion 132 and guiding arm 138 disposed on lower portion 134.As described in further detail below, the cannula may have clips andwings sized and shaped to interact with ledges 128 and guiding arms 138and 140 such that the cannula is advanced into the skin of the wearer ina substantially linear direction and with minimal rotation.

Internal component 114 (e.g., at lower portion 134) further may includeblocking mechanism 130, which is configured to interact with the biasingmember and links such that, in an initial state, blocking mechanism 130prevents rotation of the links. Attachment pad couplers 124 may interactwith corresponding locking mechanisms of the pad skeleton to lock theapplicator to the pad. For example, attachment pad couplers 124 may becoupled to the pad attachments at the first end of the pad. Attachmentpad couplers 124 may be extensions (e.g., arms) that extend toward thepad. Further, attachment pad couplers 124 preferably are flexible suchthat contact from the cannula moves attachment pad couplers 124 awayfrom the position that locks the applicator to the pad during cannuladelivery.

Referring now to FIG. 6 , operation of the internal component andmechanism for inserting the cannula is described. In FIG. 6 , internalcomponent 114 is shown in a pre-assembled state. Lower portion 134 mayinclude axis 146 around which link 118 is designed to rotate. Biasingmember 116 extends around and along axis 146. Biasing member 116 biaseslink 118 to rotate about axis 118. Prior to actuation, blockingmechanism 130 contacts and holds link 118 in place. Upon actuation bythe wearer, blocking mechanism 130 moves relative to link 118 such thatblocking mechanism 130 no longer contacts link 118, thereby allowingforce applied by biasing member 116 to cause one or more links to rotateand advance the cannula and needle distally, through the skin of thewearer. Link 118 may be coupled to biasing member 116 such that link 118cannot move relative to biasing member 116. In a pre-deployed state,biasing member 116 may be biased in a direction (e.g., clockwise) suchthat link 118 applies a force to blocking mechanism 130 in a differentdirection (e.g., opposite, counterclockwise). Link 120 may be coupled tolink 118 via joint 142 and applicator needle 150 may be coupled to link120 via joint 144. In a pre-deployed state, joint 144 may be disposedadjacent to cannula interface 148 and applicator needle 150 may bepositioned within a lumen of cannula 200. Applicator needle 150 may besized and shaped such that the distal end of applicator needle 150extends past the distal end of cannula 200. Applicator needle 150 mayhave an angled tip that is configured to minimize the risk of hittingpad skeleton 104 or applicator housing 110 during insertion of cannula200. Cannula 200 may be disposed within channel 126 and may beconfigured to slide in a distal direction along ledges 128, throughchannel 126, and through the skin of the wearer.

Referring now to FIGS. 7A-7D, operation of the mechanism and steps forinserting the cannula are described. The applicator is configured toinsert cannula 200 via rotational movement of the insertion mechanism ofthe applicator. This rotational movement provides several benefits overthe mechanisms employed in previously known devices, including, forexample, minimizing hard stops, thus reducing the noise of theapplicator. FIG. 7A depicts the applicator in a pre-deployed state. Pad102 is partially cut near the location of insertion of cannula 200 inFIGS. 7A-7D to better show how cannula 200 and applicator needle 150 aredeployed. Biasing member 116 is biased in a clockwise direction andblocking mechanism 130 is disposed in a position that prevents link 118,which is coupled to biasing member 116, from moving in acounterclockwise direction. As will also be understood by one ofordinary skill in the art, biasing member 116 may instead be biased in acounterclockwise direction such that, upon actuation, link 118 rotatesin a clockwise direction.

The applicator may include a needle configured to pierce the skin of thewearer, and to provide a path for cannula 200 to advance through theskin. Alternatively, as described further below, a portion of cannula200 may instead be used to pierce the wearer's skin. Applicator needle150 may be disposed within the lumen of cannula 200 and may extend fromcannula head 204, through elongated shaft 202, and past cannula tip 218.In the pre-deployed state, cannula head 204 preferably is disposed atthe proximal end of channel 126 such that cannula 200 is disposedentirely within applicator housing 110. Cannula 200 may include one ormore clips 206 disposed on cannula head 204, which are configured toguide cannula 200 in a substantially linear direction. Clips 206 mayextend outward from cannula and may be two wings disposed on either sideof cannula head 204 and sized and shaped to slide along ledges 128.Preferably, in the pre-deployed state, cannula tip 218 is disposed nearpad 102, between pad attachments 106, such that clips 206 may be coupledto pad attachments 106 advancement of cannula 200.

FIG. 7B depicts the applicator in a partially-deployed state, whereincannula 200 is inserted into the skin of the wearer, but applicatorneedle 150 is not yet withdrawn. Upon actuation of actuator 112, adownward force is applied to internal component 114, which causes lowerportion 134 to deflect. The downward force on blocking mechanism 130transitions blocking mechanism 130 to a position beneath link 118 suchthat link 118 is able to freely rotate. Because biasing member 116 isbiased in a clockwise direction and is coupled to link 118, link 118then rotates about axis 146 in a counter-clockwise direction. Therotation of link 118 causes link 120, which is coupled to link 118 viajoint 142, to move distally and apply a distal force to applicatorneedle 150 and cannula 200. Applicator needle 150 and cannula 200 areconfigured to move in a distal direction through channel 126 such thatthe distal end of applicator needle 150 pierces the skin of the wearerand at least a portion of cannula 200 is inserted. Preferably, clips 206are disposed on cannula head 204 such that clips 206 slide along ledges128, guiding cannula 200 and applicator needle 150 in a substantiallylinear direction.

As described further below, when cannula 200 is inserted, the proximalend of cannula 200 preferably is coupled to one or more pad attachmentsdisposed on the pad skeleton in order to lock cannula 200 to the pad. Atthe same time that cannula 200 is coupled to the pad skeleton, theapplicator may be uncoupled from pad skeleton in a single actuation.

In FIG. 7C, the applicator is depicted in a fully-deployed state,wherein cannula 200 is inserted into the skin of the wearer andapplicator needle 150 is withdrawn. After cannula 200 is inserted,biasing member 116 may continue to apply a force to link 118 such thatlink 118 continues to rotate in a counter-clockwise direction, forcinglink 120 to move in a proximal direction. Preferably, cannula 200remains coupled to the pad skeleton and applicator needle 150 remainscoupled to link 120 via joint 144 such that cannula 200 and applicatorneedle 150 are separated. As link 120 moves in a proximal direction,applicator needle 150 is withdrawn from cannula 200 and into theapplicator, at least a portion of cannula 200 remaining in the wearer'sskin. The withdrawal of applicator needle 150 into the applicatorensures the needle is stored in a safe, remote place.

Referring to FIG. 7D, the applicator is depicted in a fully-deployedstate, wherein applicator needle 150 is stored within applicator housing110, biasing member 116 is completely unloaded, and the rotation of link118 is stopped. Links 118 and 120 and applicator needle 150 may stoprotating without contacting any surfaces. Internal component 114 mayinclude one or more stopping zones that are configured to allow slowingof the rotation of links 118 and 120. For example, internal component114 may include upper stopping zone 152 and lower stopping zone 154.Upper stopping zone 152 may be positioned at the proximal end ofinternal component 114, where joint 142 is configured to stop rotatingwhen biasing member 116 is completely unloaded. Lower stopping zone 154may be distal to upper stopping zone 152, where joint 144 is configuredto stop rotating when biasing member 116 is completely unloaded.

Referring now to FIG. 8 , operation of the lower stopping portion whenthe applicator withdraws the needle is described. To further reduce thenoise from inserting the cannula, lower stopping portion 154 may clampjoint 144 between two surfaces to help slow the rotation of link 120 andapplicator needle 150. As shown in FIG. 6 , the biasing member, links118 and 120, and applicator needle 150 are disposed between upperportion 132 and lower portion 134. Upper portion 132 and lower portion134 may each have a sloped section that narrows the space between theupper and lower portion. When joint 144 reaches lower stopping portion154, joint 144 becomes clamped between upper portion 132 and lowerportion 134, such that link 120 and applicator needle 150 are preventedfrom continuing to rotate.

With respect to FIGS. 9A and 9B, an exemplary pad for attaching the pumpto a wearer is described. Pad 102 is attached to the wearer and isconfigured to support the applicator, the patch pump, and the cannula.Pad 102 comprises a first surface, on which pad skeleton 104 isattached, and a second, skin-facing surface that includes pad adhesive105 that is safe to apply to skin. Pad adhesive 105 is configured tosecure the pad to the wearer for a period of at least 3-10 days andpreferably is strong enough to hold the patch pump on the wearer duringthe wearer's normal, daily motions including showering, swimming, andother outdoor activities. One or more release liners 103 may be attachedto pad adhesive 105 until pad 102 is ready to be secured to the wearer.FIG. 9B shows release liners 103, which have been partially cut at thelocation of cannula insertion. Pad skeleton 104 is configured to couplepad 102 to the applicator for insertion of the cannula and to the patchpump for delivery of the medication. Pad skeleton 104 may include one ormore locking mechanisms configured to lock the applicator, the pump-capassembly, and/or the cannula to pad skeleton 104. For example, padskeleton 104 may include pad attachments 106 at a first end of pad 102,pad back clip 108 at a second end of pad 102, and one or more pad clipsholes 107 at one or more sides of pad 102.

Referring now to FIGS. 10A-10F, further details of the applicator, pad,and cannula are described. The applicator and pad may be configured toboth insert the cannula and cause the cannula to be locked to the pad ina single actuation. Preferably, pad 102, which is shown as partially cutin FIGS. 10A, 10B, and 10D to better show how cannula 200 and applicatorneedle 150 are deployed, includes one or more locking mechanisms thatmay be configured to lock to either the applicator, cannula, and/or thepump-cap assembly. For example, pad 102 may include pad attachments 106,as described above, and the applicator may include flexible attachmentpad couplers 124, which are configured to fit within one or more slotsof pad attachments 106. In the pre-deployed state, attachment padcouplers 124 are disposed within the slots of pad attachments 106 suchthat the applicator is coupled to pad 102 via pad skeleton 104, as shownin FIG. 10A.

Upon actuation by the wearer, the cannula is configured to advancedistally, through the skin of the wearer. As shown in FIG. 10C, cannula200 may include one or more clips 206 disposed on cannula head 204 andconfigured to interact with channel 126 of the applicator and guidecannula 200 in a substantially linear direction during insertion.Cannula head 204 may further include one more wings 207 configured toprotrude towards the wearer's skin and to interact with guiding arm 138to order to prevent cannula 200 from rotating around the longitudinalaxis of cannula 200 during and after insertion. As described below withrespect to FIGS. 12A and 12B, control of the orientation of the cannulain the wearer's skin is important to ensure precise delivery ofmedication through the aperture(s).

Clips 206 preferably are also configured to function as a lockingmechanism. For example, clips 206 may be one or more protrusionsdisposed on a first and second side of cannula head 204. In the deployedstate, clips 206 may be disposed within the slots of pad attachments 106such that the cannula is coupled to pad 102 via pad skeleton 104, asshown in FIG. 10B. This single actuation both locks the cannula to pad102 and pushes attachment pad couplers 124 away from the slots of padattachments 106, unlocking the applicator to pad 102. Once theattachment pad couplers 124 are uncoupled to pad attachments 106, theapplicator may be removed from the wearer's skin, leaving pad 102 andthe cannula in place, as shown in FIGS. 10D-10F.

In order to maintain the proper orientation of the cannula, wings 207are preferably sized and shaped to fit between two pad attachments 106,as shown in FIG. 10E, and clips 206 are preferably sized and shaped tofit within the slots of pad attachments 106, as shown in FIG. 10F. Padskeleton 104 may further include angled interface 101, which may bedisposed between pad attachments 106 and shaped to have an interface atthe angle the cannula is inserted such that angled interface 101 engageswith cannula head 204 in the deployed state. Ensuring a proper fit ofcannula 200 to pad skeleton 104 prevents rotation or other movement ofthe cannula after insertion, resulting in accurate delivery ofmedication. After the applicator is removed, the pump-cap assembly maybe coupled to the pad-cannula assembly via pad clips holes 107.

Referring now to FIG. 11A, further aspects of the applicator, pad, andcannula are described. In FIG. 11A, the applicator is depicted in apartially-deployed state, wherein the cannula is inserted into the skinof the wearer, but applicator needle 150 is not yet withdrawn. Thedistal end of applicator needle 150 may be disposed distal to cannulatip 218 and the proximal end of applicator needle 150 may be coupled tolink 120. Applicator needle 150 preferably is inserted through theseptum of the cannula and extends past the distal end of the cannula.Septum 224 is a self-sealing material designed to seal the proximalregion of the cannula, such as silicone, and minimizes backflow out ofthe cannula. Septum 224 may be disposed within cannula head 204 andsupports and guides applicator needle 150 such that the needle iswithdrawn in a substantially linear direction. Applicator needle 150 maybe coupled to link 120, which interacts with applicator interfaces 220and 222 disposed on cannula head 204 and configured to provide smoothand continuous contact with link 120 during insertion of the cannula.After the cannula is inserted, cannula head 204 of the cannula may belocked to pad attachments 106, as shown in FIG. 10B. Elongated shaft 202of the cannula extends from pad attachments 106, past pad skeleton 104,through pad 102, and into the skin of the wearer. Depending on the typeof medication inserted (e.g., insulin), the cannula may be inserted suchthat apertures 208, 210, 212, and 214 and cannula tip 218 are disposedbelow the dermal layer of skin.

With respect to FIG. 11B, interengagement of the pad and an exemplarypatch pump is described. After the cannula is deployed and is coupled topad 102 via pad attachments 106, as shown in FIG. 10B, the applicator isremoved from pad 102. A patch pump constructed in accordance with theprinciples of the present invention, which preferably includes adisposable cap and a reusable pump, is coupled to pad 102 to delivermedication via the cannula. For example, the patch pump may include ahousing that is configured to lock to pad skeleton 104 such that thepatch pump is secured to the wearer during the wearer's normal, dailymotions. The patch pump may include outflow needle 408, which is influid communication with the cannula and to deliver a predetermined doseof medication from a cartridge to the cannula responsive to pumping atthe patch pump. Outflow needle 408 preferably is configured to pierceseptum 224 of cannula head 204 such that the distal end of outflowneedle 408 is disposed below septum 224 and medication flows intoelongated shaft 202, rather than back into the patch pump, fortranscutaneous delivery to the wearer via one or more apertures of thecannula. Further, as illustrated, the entirety of cannula head 204 maybe designed to stay above the skin line and remain external to thepatient while elongated shaft 202 is transcutaneous.

Cannula for Delivering Medication

Referring now to FIGS. 12A and 12B, an exemplary cannula for deliveringmedication is described. Cannula 200 may be injection molded from asingle piece of material, which is preferable to extrusion in order toreduce the risk of kinking of cannula 200. Cannula 200 preferably ismade from a material that is insulin compatible and flexible andincludes cannula head 204, cannula tip 218, and elongated shaft 202.Cannula head 204 is disposed at the proximal end of cannula 200 andconfigured to interact with the applicator needle and the needle throughwhich the medication is delivered. Cannula tip 218 is disposed at thedistal end of cannula 200 and may include distal aperture 216 fordelivering medication. Elongated shaft 202 may extend between cannulahead 204 and cannula tip 218 and may include one or more apertures fordelivery of medication. Elongated shaft 202 may increase in diametertowards cannula head 204 and the wearer's skin surface, to mitigate therisk that the delivered medication travels proximally along the outsidesurface of the cannula to the dermal layer or the surface of the skin.This conical shape may also reduce the risk of kinking of cannula 200.

Elongated shaft 202 also may have one or more apertures disposed alongthe elongated shaft in any configuration. Preferably the apertures aredisposed such that medication is delivered only below the dermal layerof the skin. As depicted in FIG. 12A, cannula 200 may include aperture210 and aperture 214, disposed distal to aperture 210, which areoriented towards the skin surface of the wearer. As shown in FIG. 12B,cannula 200 also may include aperture 208 and aperture 212, which areoriented away from the skin surface of the wearer. As will also beunderstood by one of ordinary skill in the art, the cannula may beconfigured such that the apertures are axially oriented relative to adifferent target infusion area within the wearer.

Cannula head 204 may include one or more applicator interfaces that areconfigured to interact with link 120 to permit rotational movement ofthe cannula during insertion of the cannula into the skin of the wearer.For example, applicator interface 220 may be disposed on the side ofcannula head 204 that is farthest away from the skin surface of thewearer. Applicator interface 220 may be a rounded, convex protrusion,which interacts with a corresponding rounded, concave receptacle of link120. Cannula head 204 also may include applicator interface 222, whichmay be disposed on the opposite side of the cannula head, the sideclosest to the skin surface of the wearer. Applicator interface 222 maybe a rounded, concave receptacle, which interacts with a correspondingrounded, convex protrusion of link 120. The rounded shapes of applicatorinterfaces 220 and 222 and the corresponding features of link 120 aredesigned such that link 120 maintains smooth and continuous contact withcannula head 204 during insertion of cannula 200 into the wearer's skin.

Cannula head 204 also may include one or more clips 206 configured toguide cannula 200 in a substantially linear direction. Clips 206 may beany component of cannula head 204 that is configured to interact withthe channel of the internal component of the applicator during insertionof cannula 200 into the wearer's skin. For example, clips 206 may be oneor more wings disposed on a first and second side of cannula head 204and sized and shaped to slide along the ledges of the channel. Clips 206alternatively may be receptacles disposed on cannula head 204 andconfigured to slide along corresponding protrusions of the channel.Cannula head 204 may further include wings 207, which may be configuredto interact with the guiding arm to order to prevent cannula 200 fromrotating around the longitudinal axis of cannula 200 during and afterinsertion. Preferably, wings 207 are configured to protrude towards thewearer's skin and the guiding arm and are sized and shaped such that theguiding arm fits between the two wings. Clips 206 and wings 207 aredesigned to control orientation of the cannula during delivery andinsertion. Because the apertures along the shaft of the cannula may beradially and longitudinally offset from one another, control of theorientation of the cannula in the wearer's skin is important to ensureprecise delivery of medication through the aperture(s). Thus, clips 206and wings 207 ensure axial orientation in a target direction of theapertures.

Referring to FIGS. 13A and 13B, alternative embodiments of the distalend of the cannula are described. In FIG. 13A, cannula tip 218 has anangled tip for inducing curvature in the cannula during insertion.Preferably, the cannula is curved towards the surface of the skin, whichpermits the cannula to have a greater length without being inserted toodeep within the wearer's skin. The greater the length of the cannula,the more apertures that may be positioned along elongated shaft 202,which may extend the life of the cannula. Further, the angled tip may beoriented such that the distal portion of the angled tip is configured tobe oriented nearer the skin surface than the proximal portion of theangled tip.

FIG. 13B depicts an alternative embodiment of the distal end of thecannula, which includes one or more knife blades 226, which areconfigured to reduce the pain from insertion of the cannula and maintainthe preferred axial orientation of the cannula during and afterinsertion. Knife blades 226 may extend proximally from cannula tip 218along a portion of elongated shaft 202. Knife blades 226 have sharpenededges to facilitate piercing the skin and insertion of the distal end ofthe cannula. Preferably, two knife blades disposed on opposing sides ofthe cannula shaft, adjacent to the distal end, may be employed.

Turning to FIG. 14A, an embodiment of a cannula having multipleapertures is described. The apertures are preferably arranged in aconfiguration that ensures the medication is delivered to theappropriate location within the wearer's skin. The multiple aperturesalso may be arranged such that medication is delivered along the lengthof elongated shaft 202. The cannula may include cannula head 204,cannula tip 218, and elongated shaft 202. Cannula head 204 may includeseptum 224, which is configured to both support the applicator needleduring insertion of the cannula into the wearer's skin and to supportthe needle of the patch pump during delivery of the medication. Theapplicator needle is disposed through septum 224 during the insertion ofthe cannula into the wearer's skin.

The cannula may have several apertures for delivery medication, suchthat medication is delivered only below the dermal layer of skin. Distalaperture 216 may be disposed at cannula tip 218 and four apertures maybe disposed along elongated shaft 202. Apertures 208 and 212 aredisposed on the side of elongated shaft 202 oriented away from the skinsurface of the wearer and apertures 210 and 214 are disposed on the sideof elongated shaft 202 oriented towards to the skin surface of thewearer. Aperture 208 may be the proximal most aperture such thatmedication delivered through aperture 208 is delivered in the directionaway from the skin surface of the wearer. This configuration ofapertures mitigates the risk of delivering medication into the dermalayer of the wearer's skin. Delivery below the dermal layer of skin isparticularly important for insulin delivery in order to ensure stableabsorption. As described above, clips 206 and wings 207 may be used toensure a desired orientation of cannula shaft during and after insertionto align the apertures in the desired manner.

With respect to FIGS. 14B-14E, alternative embodiments of cannulacomprising biodegradable materials are described. The use ofbiodegradable materials within the cannula expands the insulin infusionarea and volume over time. One of the main issues with previously knowncannula is the risk of occlusion, which occurs when insulin reacts withfat. The typical life of a cannula with a single aperture at the distalend (e.g., distal aperture 216) is about 3-4 days. The addition ofbiodegradable materials that dissolve to open additional apertures overtime may extend the life of the cannula to at least 7-10 days. Thegreater the life of the cannula, the fewer times the wearer is requiredto insert a new cannula into their skin at a different location and theless waste created from used cannulas.

The biodegradable materials may either be disposed within the lumen ofthe cannula (“lumen plug”) or within the apertures of the cannula(“aperture plug”) such that medication may still travel through thelumen and distal aperture 216. The biodegradable materials preferablyhave fast degradation rates, e.g., several days. Exemplary biodegradablematerials include: polysaccharide-based materials; salt; silk;hyaluronic acid (HA); polyethylene glycol (PEG); saturated aliphaticpolyesters:poly(lactic acid) (PLA), polyglycolide (PGA), combinationthereof (poly(lactide-co-glycolide), PLGA); polyanhydrides.

The cannula of FIG. 14B includes two types of lumen plugs in an initialstate. First biodegradable material 230 and second biodegradablematerial 232 may be disposed within elongated shaft 202 and block one ormore apertures. First biodegradable material 230 may have a shorterdissolution time than second biodegradable material 232. For example,first biodegradable material 230 may have a dissolution period of 2-3days and second biodegradable material 232 may have a dissolution periodof 4-6 days. First biodegradable material 230 preferably is disposeddistal to the proximal-most aperture (e.g., aperture 208) such that, inthe initial state, medication may be delivered through the proximal-mostaperture. First biodegradable material 230 may block one or moreapertures along elongated shaft. For example, first biodegradablematerial 230 preferably blocks aperture 210 but does not block apertures212 or 214 or distal aperture 216.

As shown in FIG. 14C, after first biodegradable material 230 dissolves,aperture 210 is opened and second biodegradable material 232 remainsdisposed within the lumen of the cannula. Second biodegradable material232 may be disposed distal to first biodegradable material 230 andpreferably blocks apertures 212 and 214 and distal aperture 216. Aftersecond biodegradable material 232 dissolves, all of the apertures of thecannula may be opened. Over time, the apertures through which medicationis initially delivered may become occluded due to the reaction betweenthe delivered insulin and the fat. However, the dissolution of thebiodegradable materials at varying times mitigates this issue byperiodically opening new apertures.

In the cannula plug embodiment of FIGS. 14B and 14C, a modifiedapplicator needle and method for inserting the cannula may be necessary.For example, the applicator needle may be shortened such that it doesnot extend through any biodegradable material. If the applicator needledoes not extend past the distal tip 218, the distal-most cannula plug,second biodegradable material 232, preferably is configured to have asharp distal end that is configured to pierce the wearer's skin.

With respect to FIGS. 14D and 14E, a cannula having two types ofaperture plugs in an initial state is described. Third biodegradablematerial 234 and fourth biodegradable material 236 may be disposedwithin the apertures on elongated shaft 202 such that medication maystill travel through the lumen and distal aperture 216, which remainsunblocked. Third biodegradable material 234 may have a shorterdissolution time than fourth biodegradable material 236. For example,third biodegradable material 234 may be similar to first biodegradablematerial 230 and may have a dissolution period of 2-3 days. Fourthbiodegradable material 236 may be similar to second biodegradablematerial 232 and may have a dissolution period of 4-6 days. Thirdbiodegradable material 234 preferably is disposed within apertures 212and 214 and fourth biodegradable material 236 preferably is disposedwithin apertures 208 and 210. As the delivered insulin reacts with fat,potentially occluding distal aperture 216 and apertures 212 and 214,fourth biodegradable material 236 will dissolve, opening apertures 208and 210.

As will also be understood by one of ordinary skill in the art, thecannula may include only one biodegradable material or may include morethan two biodegradable materials. In the lumen plug embodiment, thebiodegradable materials may be configured to block one or moreapertures. In the aperture plug embodiment, the biodegradable materialsmay be configured to block different apertures than illustrated. As willalso be understood, biodegradable materials may have a dissolutionperiod of 0-10 days, and the choice of biodegradable material may dependupon the configuration of the biodegradable materials and the number ofdifferent types of biodegradable materials incorporated into thecannula.

Reusable Patch Pump and Disposable Cap for Delivering Medication

Referring now to FIGS. 15A and 15B, perspective views of an exemplarypatch pump and pump-cap assembly constructed in accordance with theprinciples of the present invention are described. The patch pump isconfigured to attach to the adhesive pad secured to the wearer and todeliver doses of medication through the inserted cannula. The patch pumppreferably includes a reusable pump, a disposable cap, a disposablepre-filled cartridge of medication, and a pad. The pump is configured tobe used for several years, thus reducing waste as well as the cost ofthe system. The user preferably may own two reusable pumps, which allowsthe user to recharge the first pump while wearing and receivingmedication from the second pump. As described above, the first pump maycommunicate data to or from the second pump, so as to provide continuityof insulin infusion when one pump is changed out for the other pump. Thewearer may alternative using two pumps such that one pump is the centerof the configuration data system controlling, among other things, theinsulin delivery process, the heart rate measurement process, theglucose measurement process, the authentication of the pumps to eachother, and the authentication of the user's smartphone, theauthentication of the user, and the authentication of the physician. Atany given time no or only one pump is active. The pumps share theirconfiguration data when possible, either directly with the other pump orvia a file temporarily stored in the patient's smartphone. The data maybe secured by encryption and authenticated by a signature, bothoperations using the best standards in the field. The data may betransferred from the active pump to the non-active pump. Preferably,only the active pump can change the configuration via instructions givenby the wearer or the physician.

The patch pump may include pump 300 preferably designed to be used foran extended period of time (e.g., 2-4 years), and cap 400 preferablydesigned to be replaced after a much shorter period of time (e.g., 3-5days). The patch pump also may include a pre-filled cartridge ofmedication, such as cartridge 500, which may be filled duringmanufacturing or by the wearer prior to inserting cartridge 500 into thepump. For example, the wearer may pre-fill several cartridges configuredto last one month and store the pre-filled cartridges in the fridgeuntil the cartridge are to be used. The patch pump may be configuredsuch that the pre-filled cartridges may be inserted into the patch pumpas soon as the cartridges are removed from the fridge. For example, thepatch pump may complete an initialization process, described furtherbelow, which reduces the formation of bubbles within the cartridge.Preferably, the wearer need not wait a certain period of time (e.g., 20minutes) before inserting the cartridge into the patch pump. Cartridge500 may include a cartridge cap through which an inflow needle of cap400 is disposed and a plunger, disposed at the opposite end andconfigured to be advanced toward the cartridge cap to deliver insulin.Cartridge 500 is configured to be inserted into the patch pump such thatcartridge 500 is completely enclosed within the patch pump. For example,cartridge 500 may be inserted first into pump 300 such that a portion ofcartridge 500 remains outside of pump housing 302. Cap 400 then may becoupled to cartridge 500 such that an inflow needle disposed within cap400 pierces the cartridge cap of cartridge 500. While still maintaininginflow needle within cartridge 500, cap 400 then may be rotated relativeto pump 300 to lock cap 400 to pump 300, thereby coupling the cap-pumpassembly to the pad and the pump.

Pump 300 may include a motor disposed within pump housing 302, the motorconfigured to move a pusher coupled to the plunger of cartridge 500 suchthat insulin is advanced through an inflow needle of cap 400 and to amicrodosing system designed to measure and deliver predetermined dosesof medication. The same motor may simultaneously activate the plunger ofthe cartridge and the microdosing system, for example, via a gearbox.Doses of medication may be delivered to the user responsive to operationof a processor, in accordance with programming stored in memoryassociated with the processor or specifically when requested by theuser, e.g., using a suitable wireless application on the user'ssmartphone. The processor may be configured to monitor one or moresensors and modify operation of pump 300 or alert the wearer based oninformation sensed by one or more sensors.

Cap 400 is configured to receive medication from cartridge 500 anddeliver predetermined doses of the medication through an outflow needle,into cannula 200, and to the wearer. Cap 400 preferably includes amicrodosing system configured to measure and deliver the predetermineddoses of medication. Cap 400 further may include locking mechanismsconfigured to lock cap 400 to pump 300 such that cartridge 500 iscompletely enclosed within pump housing 302 and cap housing 402 in aclosed and locked position. Cap 400 may include additional lockingmechanisms configured to lock the pump-cap assembly to the pad. Forexample, cap 400 may include one or more cap clips 403, which may besized and shaped to fit within one or more pad clips holes disposed onthe pad skeleton. The pump-cap assembly may be unlocked from the pad bypressing unclipping buttons 405, which preferably are configured todeflect cap clips 403 such that cap clips 403 may be removed from thepad clips holes. This method of locking and unlocking the pump-capassembly to the pad ensures that the patch pump will remain in placeduring the wearer's daily motions and is convenient for the wearer tosecure and remove the pump-cap assembly. For example, the wearerpreferably can clip/unclip the pump-cap assembly from the pad using onehand, even if the patch pump is secured to a difficult to reach area ofthe body, such as the back of the arm.

Referring to FIG. 16 , the lower side of the assembled patch pump isdescribed. The patch pump includes pump housing bottom 305, which is thelower side, or skin-facing side, of the pump that is oriented toward thewearer's skin. Pump housing bottom 305 may be coupled to pump housing302, which is an upper side of the pump that is oriented away from thewearer's skin. Pump housing bottom 305 may have a slight concavity suchthat the patch pump maintains contact with the wearer's skin. The patchpump preferably includes reusable pump 300 having pump housing 302 anddisposable cap 400 having cap housing 402, which are coupled togetherwith the pad to form the patch pump. Cap 400 further may includeconnection cavity 404, sized and shaped to receive the pad attachmentsand cannula head, which protrude from the pad and lock the cannula tothe pad, when the patch pump is locked to the pad. Connection cavity 404may house an outflow needle that is configured to interact with thecannula. Cap 400 may include one or more cap clips 403, which may becoupled to one or more unclipping buttons 405 that may be pressed tounlock the pump-cap assembly from the pad. Preferably, the cap includestwo unclipping buttons 405 disposed on each side of the cap, eachunclipping button 405 having two cap clips 403 that are sized and shapedto fit within the pad clips holes disposed on the pad skeleton, therebyallowing lateral clipping.

Pump 300 may include a photoplethysmography sensor configured todetermine the wearer's heart rate or other physiologic parameters, whichmay be used to adjust the delivery of medication from pump 300 to thewearer, as described in U.S. Pat. No. 11,241,530 to Fridez et al. andPCT International Application No. PCT/IB2021/060766, the entire contentsof each of which are incorporated herein by reference. For example,using physical activity level, or a determination that the wearer issleeping or awake, a small change may be made in an algorithm thatcontrols an amount or rate of insulin injection, which couldsignificantly influence blood glucose level. The patch pump controlleralso could use heart rate, as determined by the photoplethysmographysensor, to implement a sport mode, for example, that permits a slightlyhigher glucose target to decrease the risk of hypoglycemia afterphysical exertion.

The photoplethysmography sensor may be electrically coupled to a circuitboard disposed within pump 300 and may be disposed withinphotoplethysmography sensor frame 304, which is disposed on theskin-facing side of pump housing 302. Photoplethysmography sensor frame304 may extend through a pad opening in the pad attached to the wearer.The skin-facing side of pump housing 302 preferably is configured toinclude one or more protrusions such that the photoplethysmographysensor maintains contact with the wearer's body surface during motion,while also reducing cross talk between emitters and detectors and fromambient light impinging upon the photoplethysmography sensor. Forexample, the skin-facing side of pump housing 302 may include optionalrib 308, configured to protrude from pump housing 302 to block light.Rib 308 may surround bump 310, which houses the photoplethysmographysensor. Bump 310 preferably protrudes farther from pump housing 302 thanrib 308, such that bump 310 maintains contact with the wearer's skinwhile ensuring that the contact force of bump 310 does not applyexcessive pressure to the wearer's skin or cause tissue necrosis.

The photoplethysmography sensor is designed to generate a strongphotoplethysmography signal suitable for heart rate monitoring and pulseoximetry and may include one or more LEDs and one or more detectors. Thephotoplethysmography sensor may include an exemplary multi-chipphotoplethysmography package suitable for use in the patch pump, forexample, the SFH 7072 BIOFY® Sensor device commercially available fromOSRAM Opto Semiconductors GmbH, Regensburg, Germany. The multi-chipphotoplethysmography package may include red, infrared, and green LEDs,an infrared cut detector to detect reflected light from green LEDs, anda broadband detector to detect reflected light from red and infraredLEDs. Preferably, the red LED has a centroid wavelength of 655 nm, theinfrared LED has a centroid wavelength of 940 nm and the green LEDs havea centroid wavelength of 530 nm. The LEDs and detectors are set in aceramic package that includes one or more light barriers configured toreduce optical crosstalk between the LEDs and detectors.

As is well known in the photoplethysmography art, green LEDs arecommonly used in monitoring heart rate in wearables in view of theirgood signal-to-noise ratio and resistance to motion artifact, while thecombination of red and infrared LEDs provides accurate monitoring ofblood oxygen saturation. Suitable algorithms are known in the art forprocessing photoplethysmographic signals generated with red and infraredLEDs and green LEDs to reduce the effects of motion noise, includingfrequency domain analysis and Kalman filter analysis techniques.Alternatively, infrared-red LEDs may be used, instead of the green LEDs,to compute heart rates for wearers having darker skin complexions. Aswill also be understood by one of ordinary skill in the art, more orfewer LEDs advantageously could be employed in the photoplethysmographysensor.

Photoplethysmography sensor frame 304 preferably includes one or moretransparent windows 306 and a layer, forming bump 310.Photoplethysmography sensor frame 304 may comprise a sturdybiocompatible plastic or rubber material that may have one or moreopenings. Windows 306 may consist of a clear plastic material having lowabsorptivity for light at the wavelengths of the LEDs and may beconfigured to mate with the openings of photoplethysmography sensorframe 304 to provide a smooth exterior surface for bump 310. The layerpreferably is a closed cell foam or similar compressible materialagainst which the photoplethysmography sensor is urged against the layerinto contact with windows 306. Photoplethysmography sensor frame 304 andthe layer preferably are matte black or gray to reduce light scatteringof light reflected from tissue through windows 306. Window 306 may be asingle thin window <0.5 mm thick or, alternatively may include more thanone window.

Heart rate signals generated by the photoplethysmography sensor may beused by the controller to modulate infusion of insulin from the patchpump. Preferably, the photoplethysmography sensor periodically measuresthe wearer's heart rate, e.g., once every minute, 2½ minutes or fiveminutes, and computes a heart rate and a quality measure for thecomputed heart rate. The quality measure may be used to determinewhether to adjust insulin delivery to better maintain the stability ofthe wearer's blood glucose level.

In addition, the heart rate data may be used to compute an activityintensity level, similar to that employed in physical activity monitors,such as resting, passive behavior, and low, medium and high levels. Suchan activity level could be used to adjust parameters of the insulindelivery algorithm to permit a “sport mode” that adjusts insulindelivery to reduce the risk of hypoglycemia during, and especiallyafter, engaging in vigorous or sports activities. The heart rate alsocould be evaluated to determine whether the wearer is asleep or awake.For example, when a wearer is asleep, the parameters of the infusionalgorithm used in the controller could be switched to a sleep mode. Thissleep mode may allow fine-tuning of the wearer's glucose level to allowprovide better sleep well and improve time in a targeted glucose range.Such adjustments are expected to be possible because while sleeping, thewearer does not eat, is not physically active, and is not physically oremotionally stressed.

Determination that a wearer is asleep or awake additionally could bebased on, or confirmed by, data from an accelerometer. Accelerometeroutputs also could be analyzed to assess where the patch pump is beingworn by the user, and to determine body orientation. The sleep/wakeinformation also may be analyzed to provide a quality measure of themeasurement, and thus allow the infusion algorithm employed by thecontroller to have a good degree of confidence regarding its insulindelivery adjustments. The output of the photoplethysmography sensor alsomay be used to validate that the patch pump is adequately adhered to thewearer's skin to allow insulin injection, as described further below.If, for example, patch pump includes a capacitive circuit forcontinuously detecting that the pump is adhered to a wearer's skin, thephotoplethysmography sensor could provide confirmation that the pump islocated on the wearer's skin.

Referring now to FIG. 17 , internal components of an exemplary pump aredescribed. For example, pump 300 may include within pump housing 302 andpump housing bottom 305 the following components: coil 312, circuitboard 314, sensor 316, battery 318, sensor 320, mechanical coupling 322,gearbox 324, sound generator 326, pump motor 328, vibration motor 330,cartridge holder 332, and/or pusher 335 (which may include screw 334,nut 336, bendable rod 338, and/or cartridge contactor 340).

Pump 300 may include housing having one or more separate pieces that areconfigured to couple together to enclose the internal components of thepump. Preferably, pump 300 includes a minimal number of parts such thatthe cost of the pump is reduced. For example, pump 300 may include pumphousing 302 coupled to pump housing bottom 305, which may includephotoplethysmography sensor frame 304. Pump housing 302 preferably has acavity to receive a portion of a pre-filled cartridge. When coupled tothe cap housing, the combined housings preferably fully enclose thecartridge. Pump housing 302 may include plethysmography sensor frame 304and pump housing back 342, which may be disposed on the end of pumphousing 302 that does not lock with the cap. Pump housing 302 also mayinclude a dry zone seal and/or one or more dry zone vents, which areconfigured to separate wet and dry zones of the pump such that theelectrical components in the dry zone are isolated from the wet zone anddo not contact any fluid and/or to permit humidity and gas to escape thehousing such that pressure may equilibrate. In addition, cartridgeholder 332 may separate the protected wet zone from the dry zone and mayinclude one or more O-rings to seal off the zones when a cartridge isdisposed within the pump-cap assembly.

Coil 312 is electrically coupled to battery 318. Coil 312 may include amagnetic shielding and preferably receives energy from outside pumphousing 302 to charge battery 318 of pump 300. For example, acorresponding coil in charging system 600 may transfer energy to coil312 to charge battery 318. The coils may be inductive coils.

Circuit board 314 permits electrical connection between electricalcomponents within pump housing 302. Circuit board has a controller withone or more processors to execute programmed instructions stored inmemory to cause motor 328 to deliver the medication to the wearer and tomonitor one or more sensed parameters generated by sensors (e.g.,sensors 316 or 320) disposed within or external to pump housing 302.

Sensor 316 is designed to sense information associated with operation ofmicrodosing system 410 and to send the information to the controller forprocessing. Sensor 316 may, for example, monitor the microdosingfunction and sense information indicative of the presence of a cap, thestatus of a cap, and/or an occlusion in the dosing pathway, as describedin detail below.

Battery 318 is a rechargeable battery to power the pump. Battery 318 hasa capacity sufficient to permit pump 300 to pump all the medication fromthe cartridge to the wearer with a single charge. Battery 318 may bedisposed within the housing and may be charged by a charger via a coilwith the charger and coil 312 within pump 300.

Sensor 320 is designed to sense information associated with operation ofpump 300 and to send the information to the controller for processing.Sensor 320 may, for example, sense information indicative of thepressure within the cartridge of medication, as described below.

Mechanical coupling 322 is designed to couple with a correspondingportion in the cap of the patch pump to translate motion from pump motor328 into components of the cap, for example, for microdosing. Mechanicalcoupling 322 further may be used for locking pump housing 302 to the caphousing. Mechanical coupling 322 is coupled to the output from gearbox324 such that mechanical coupling 322 may rotate at a reduced ratio ascompared to rotation directly output by pump motor 328.

Gearbox 324 may be coupled to motor 328, pusher 335, and/or mechanicalcoupling 322 such that rotation of the gears with gearbox 324 causesdelivery of a predetermined dose of medication to the wearer. As motor328 turns when activated, gearbox 324 causes a corresponding movement atmechanical coupling 322 and at pusher 335. Gearbox 324 incorporatesgears to change the ratio of movement pump shaft rotations of pump motor328 to generated sufficient torque to drive mechanical coupling 322 andpusher 335. For example, gearbox 324 may utilize gearing that reducesmovement generated by pump motor 328 to movement generated by mechanicalcoupling at a reduction ratio. The reduction ratio may be greater than10:1, such as 68.42:1. Advantageously, a single pump motor may be usedto both push medication out of the cartridge and move the microdosingsystem to generate the microdose of medication. For example, the singlepump motor may simultaneously (1) advance the piston with micro-stepsand (2) activate the microdosing system at every pump cycle.

Sound generator 326, responsive to instructions from the controller,generates an audible sound via a buzzer to the wearer. For example,sound generator 326 may generate the audible sound if there is an errorwith the pump or a sensed physiological parameter is beyond apredetermined threshold.

Motor 328 may be coupled to vibration motor 330, which may beoperatively coupled to the controller. The controller may cause thevibration motor to vibrate to alert the wearer based on a sensedparameter by a sensor, which may be operatively coupled to thecontroller. Preferably the controller is configured to cause vibrationmotor 330 to vibrate when the sensed parameter falls outside apredetermined threshold stored in memory. In addition, the controllermay cause vibration motor 330 to vibrate based on the controller'sdetermination that an error has occurred associated with operation ofthe patch pump based on the sensed parameter. Alternatively, thecontroller may be configured to cause vibration motor 330 to vibratebased on the time. For example, the vibration motor may vibrate onceevery three days to provide regular alerts to the user.

The sensors operatively coupled to the controller may include a sensorconfigured to sense a pressure within a cartridge, a sensor configuredto detect an occlusion in a dosing pathway, a sensor configured to sensethe temperature or humidity within the patch pump, a sensor configuredto monitor glucose levels of the wearer, a photoplethysmography sensorconfigured to sense the wearer's heart rate or physiologic parameters,or a sensor configured to sense the wearer's activity level. Thesesensed parameters may indicate whether the patch pump is runningproperly, whether the medication is stored at a safe temperature, andwhether the wearer's physiologic parameters are at a safe level.Preferably, the controller is configured to cause vibration motor 330 tovibrate when the pressure within the cartridge falls outside apredetermined pressure range, when the wearer's glucose level fallsoutside a predetermined glucose level range, when the wearer's heartrate or physiologic parameters fall outside a predeterminedphotoplethysmographic threshold, and/or when the wearer's activity levelis outside a predetermined threshold. The controller also may beconfigured to cause vibration motor 330 to vibrate when the sensordetects information indicative of an occlusion or only when the sensortwice detects information indicative of an occlusion. Additionally oralternatively, the wearer may be alerted via sound generator 326, a userinterface having LEDs, which also may be disposed within pump 300, or amobile application.

Pusher 335 is designed to push, responsive to movement from pump motor328, on an end of the cartridge. Preferably, pusher 335 pushes on aflexible plunger within the cartridge to move medication out of thecartridge during dosing. Pusher 335 also may push the plunger of thecartridge to increase pressure in the cartridge without movingmedication to the wearer, for example, during pump initialization.Pusher 335 may include screw 334, nut 336, bendable rod 338, and/orcartridge contactor 340. Screw 334 is coupled to pump motor 328, e.g.,via gearbox 324. Screw 334 may be a worm screw. Responsive to rotationalmovement at pump motor 328, screw 334 rotates in a corresponding manner(e.g., at a geared ratio). Movement of screw 334 causes nut 336 to movealong screw 334. Screw 334 may include a threaded screw and nut 336 mayinclude a threaded nut that moves along the screw responsive to rotationof the screw. Bendable rod 338 is coupled to nut 336 and moves as nut336 moves. Bendable rod 338 may curve in an approximately 180 degreeangle to cause equal and opposite movements between nut 336 andcartridge contactor 340. Cartridge contactor 340 is designed to contactthe cartridge and move the plunger of the cartridge responsive tomovement of pump motor 328. Cartridge contactor 340 may have a flangethat contacts an outer surface of the plunger at anon-insulin-contacting end. Cartridge contactor 340 also may have anextension with a smaller diameter than the flange that extends into theinner part of the plunger. In this manner, cartridge contactor may havea top hat shape.

Referring now to FIG. 18 , further aspects of the patch pump, aredescribed. The skin-facing side of the patch pump is configured tointeract with the pad and the cannula such that the patch pump issecured to the wearer and predetermined doses of medication aredelivered to the wearer. Circuit board 314, having photoplethysmographysensor 346, may be disposed within pump 300 and may be configured tocause the motor to pump the medication from the cartridge to the outflowneedle 408, which is configured to pierce the cannula. Outflow needle408 may be disposed within connection cavity 404. Connection cavity 404preferably is disposed on the skin-facing side of cap 400 and may besized and shaped to receive the proximal region of the cannula (e.g.,cannula head) such that outflow needle 408 can be coupled in fluidcommunication with the cannula to deliver the microdoses of medication.Connection cavity 404 may be sized and shaped to receive padattachments, which protrude from the pad and lock the cannula to thepad, when the patch pump is locked to the pad. The patch pump furthermay include a portion configured to hold a pre-filled cartridge ofmedication and preferably does not include a reservoir to hold multipledoses of medication separate from the pre-filled cartridge.

Turning to FIGS. 19A and 19B, an illustrative embodiment of a circuitboard is described. Circuit board 314 preferably is disposed on flexiblesubstrate 356 that can bend and fold to fit within the pump housing.Circuit board 314 includes electrical components and permits electricalcoupling between the controller and the various electrical components.One or more electrical components and/or circuits may perform some of orall the roles of the various components described herein. Althoughdescribed separately, as will be understood by one of ordinary skill inthe art, the electrical components need not be separate structuralelements. For example, a processor and wireless communication chip maybe embodied in a single chip. In addition, while the one or moreprocessor is described as having memory, a memory chip may be separatelyprovided.

Circuit board 314 may include sensor 316, sensor 320, sensor connector321, sensor 344, sensor connector 345, photoplethysmography sensor 346,sensor 348, skin detector 350, processor 352, sensor 354, flexiblesubstrate 356, skin detector 358, controller 360, motors driver 362,processor 364, wireless communication chip 366, user interface 368,sensor 369, wireless antenna 370, battery and wireless chargingmanagement 372, accelerometer 374, and/or programming connectors 376.

Controller 360 is disposed within the pump housing for controllingoperation of pump 300. For example, the controller may storeinstructions that, when executed, cause pump 300 to perform theoperations described herein. Controller 360 preferably includeselectrical components coupled on circuit board 314. Controller 360 mayinclude one or more general purpose processors, digital signalprocessors (DSP), application specific integrated circuits (ASIC), fieldprogrammable gate arrays (FPGA) or other programmable logic devices,discrete gate or transistor logic, discrete hardware components, or anysuitable combination thereof designed to perform the functions describedherein. A processor also may be implemented as a combination ofcomputing devices, e.g., a combination of a DSP and a microprocessor, aplurality of microprocessors, one or more microprocessors in conjunctionwith a DSP core, or any other such configuration.

The controller may contain memory and/or be coupled, via one or morebuses, to read information from, or write information to, memory. Thememory may include processor cache, including a multi-level hierarchicalcache in which different levels have different capacities and accessspeeds. The memory also may include random access memory (RAM), othervolatile storage devices, or nonvolatile storage devices. The storagedevices can include, for example, hard drives, optical discs, flashmemory, and Zip drives.

The processor, in conjunction with firmware/software stored in thememory may execute an operating system, such as, for example, Windows,Mac OS, Unix or Solaris 5.10. The processor also executes softwareapplications stored in the memory. In one non-limiting embodiment, thesoftware comprises, for example, Unix Korn shell scripts. In otherembodiments, the software may be programs in any suitable programminglanguage known to those skilled in the art, including, for example, C++,PHP, or Java.

In some embodiments, controller 360 may include two dedicated processorsto increase the security of the patch pump. Processor 352 may managedelivery of the medication and may monitor of one or more sensors thatmay detect sensed parameters that effect the algorithm for delivery.Processor 364 may manage the communications to and from the patch pump.

Processor 352 may be an autonomous, real time state machine thatexecutes class C software. Processor 364 may execute class B software.Preferably, processor 352 is configured such that it cannot receive datafrom outside the patch pump. For example, any communication from thewearer's mobile device or from an external continuous glucose monitoringsensor must be received by processor 364. This configuration protectsprocessor 352, and thus the delivery of medication, from any disruptionby an external device.

Processor 352 may be configured to execute first programmed instructionsstored in a first memory to cause the pump motor to pump the medicationtowards the transcutaneous portion, to monitor sensed parametersgenerated by at least one sensor, and to monitor the battery life of thebattery. For example, processor 352 may monitor sensed parametersgenerated by a sensor configured to sense a pressure within thecartridge, a sensor configured to detect an occlusion in the dosingpathway, a sensor configured to detect the wearer's skin, a sensorconfigured to detect the position of the pusher to indicate that thecartridge may be replaced, or a sensor configured to detect the positionof the cam to indicate the status of a dosing cycle.

The first programmed instructions may cause one or more components ofthe pump to move based on the sensed parameters. For example, the firstprogrammed instructions may cause the motor to push the medication inthe cartridge towards the transcutaneous portion only when a sensordetects the wearer's skin on the skin-facing side of the pump. The firstprogramming instructions also may cause the cam shaft of the microdosingsystem to stop rotating when a sensor indicates that a dosing cycle iscomplete. Further, the first programming instructions may lock or unlockthe pump, for example, when a first processor determines that the pusheris in the home position or when the first processor determines that thebattery has been sufficiently charged to a predetermined state.

Processor 364 may be configured to execute second programmedinstructions stored in a second memory to communicate data to and fromthe patch pump via the wireless communication chip. The communicateddata may include data indicative of a battery life of the rechargeablebattery or data indicative of the wearer's hear rate and physiologicparameters, which may be detected by a photoplethysmography sensor.Preferably, the second programmed instructions also use an algorithm tocalculate when to deliver the doses of medication and may adjust thecalculation based on the data received.

Wireless communication chip 366 is configured to transmit information,such as signals indicative of the sensed parameters, locally and/or to aremote location such as a server. Wireless communication chip 366 isconfigured for wireless communication over a network such as theInternet, a telephone network, a Bluetooth network, and/or a WiFinetwork using techniques known in the art. Wireless communication chip366 may be a communication chip known in the art such as a Bluetoothchip and/or a WiFi chip. Wireless communication chip 366 may include areceiver and a transmitter, or a transceiver, for wirelessly receivingdata from, and transmitting data to a remote computing device. In someembodiments, the remote computing device may be a mobile computingdevice that provides the system with a user interface; additionally oralternatively, the remote computing device is a server. In embodimentsconfigured for wireless communication with other devices, wirelesscommunication chip 366 may prepare data generated by processor 364 fortransmission over a communication network according to one or morenetwork standards and/or demodulates data received over a communicationnetwork according to one or more network standards.

Wireless communication chip 366 may be coupled to wireless antenna 370for sending and receiving information. Wireless antenna 370 may includeBluetooth antenna configured to transmit or receive signals inaccordance with established standards and protocols, such as Bluetoothand/or BLE. In some embodiments, wireless antenna 370 may be the onlymeans for the patch pump to transfer data. In some embodiments, pump 300may communicate externally as described in WO 2020/008016 or WO2020/008017, the entire contents of each of which are incorporatedherein by reference.

User interface 368 may be used to receive inputs from, and provideoutputs to, the wearer. Illustratively, user interface 368 may alert thewearer when the pressure within the cartridge is outside of apredetermined range or when an occlusion is detected or when thewearer's glucose level, heart rate, or physiologic parameters areoutside a predetermined range. User interface 368 may be coupled toprocessor 364.

User interface 368 may include a touchscreen, LED matrix, other LEDindicators, or other input/output devices for receiving inputs from, andproviding outputs to, the wearer. Alternatively, user interface 368 isnot provided on the patch pump, but is instead provided on a remotecomputing device communicatively connected to the patch pump viawireless communication chip 366. User interface 368 also may be acombination of elements on the patch pump and a remote computing device.

User interface 368 may be configured to adjust the strength of the LEDsbased on sensed parameters from sensor 369. Sensor 369 may be a lightsensor configured to detect whether the patch pump is disposed in abright or dark environment. For example, processor 352 may be configuredto adjust user interface 368 such that the strength of the LED isdecreased when it is dark and is increased when it is light.

Battery and wireless charging management 372 is configured to rechargethe battery within the pump and to ensure the safety of the battery.Battery and wireless charging management 372 may communicate with thecharging system to charge the battery and may protect against highvoltage or high current which may damage the battery. Further, batteryand wireless charging management 372 may be configured to efficientlycharge the battery and generate adequate electrical tension for circuitboard 314.

Programming connectors 376 may be provided for installing firmware inthe on-board memory of the controller attached to circuit board 314. Forexample, programming connectors 376 may be used to flash the firmware ofthe pump and may be used during development to output the signals of thesensors to determine whether circuit board 314 is working properly.Programming connectors 376 may be removed after programming, during themanufacturing of the pump.

Motors driver 362 may be used to supply current to both the vibrationmotor and the pump motor. Controlling the power supply to the motors canhave a significant effect on the noise, power consumption, and torque ofthe motors.

Circuit board 314 also may include one or more sensors configured tosense conditions within the patch pump or external to the patch pump,for example, the wearer's physiologic parameters. For example, circuitboard 314 may include sensors 316, 320, 344, 346, 348, 350, 354, 358,369, and/or 374. The sensor(s) preferably are electrically coupled tocontroller 360 (e.g., at processor 352) for monitoring and processingthe information from the sensor(s).

Sensor 316 is configured to sense information indicative of an occlusionin the dosing pathway, such as within the microdosing system or withinthe cannula. Sensor 316 preferably is electrically coupled to controller360 such that sensed signals are sent to controller 360 for processingand detecting an occlusion. Sensor 316 may be located adjacent to themicrodosing system but within the pump. In some embodiments, sensor 316is a hall-effect sensor configured detect movement of a magnet disposedon a lever of the microdosing system.

Sensor 320 may sense information indicative of the pressure within thecartridge. Sensor 320 preferably is electrically coupled to controller360 such that the sensed signals are sent to controller 360 forprocessing and detecting the pressure within the cartridge. Sensor 320may be located adjacent to the pusher and may be coupled to circuitboard 314 via sensor connector 321. Sensor connector 321 permitselectrical coupling between sensor 320 and components on circuit board314, such as the controller. In some embodiments, sensor 320 isconfigured to detect the force applied to the pusher and includes astrain gauge configured to measure deformation, for example, bymeasuring a change in electrical resistance. Controller 360 processesthis information to determine pressure within the cartridge.

Sensor 344 may sense information indicative of the status of a dosingcycle. Sensor 344 preferably is electrically coupled to controller 360such that sensed signals are sent to controller 360 for processing anddetecting whether a dosing cycle is completed. Sensor 344 may be locatedadjacent to the microdosing system but within the pump and may becoupled to circuit board 314 via sensor connector 345. Sensor connector345 permits electrical coupling between sensor 344 and components oncircuit board 314, such as the controller. In some embodiments, sensor344 detects oscillations of signals that are generated by aferromagnetic blade that may be coupled to the cam plate. In someembodiments, a dosing cycle corresponds to a ½ turn of the cam so sensor344 senses whether the ½ turn has occurred.

Photoplethysmography sensor 346 is configured to sense the wearer'sheart rate or other physiologic parameters. Photoplethysmography sensor346 preferably is electrically coupled to controller 360 (e.g., toprocessor 352 of controller 360) such that the sensed parameters aresent to controller 360 for processing and detecting whether the wearer'sheart rate or other physiologic parameters are outside a predeterminedrange. Photoplethysmography sensor 346 may be located on circuit board314 such that is disposed on the skin-facing side of the patch pump,preferably within a window of the patch pump.

Sensor 348 may sense information indicative of the position of thepusher, which may be indicative of the battery life of the rechargeablebattery, whether a new cartridge may be inserted, and/or whether thepatch pump may be unlocked. Sensor 348 preferably is electricallycoupled to controller 360 such that the sensed position is sent tocontroller 360 for processing and detecting the position of the pusher.For example, sensor 348 may indicate that a component of the pusher isat the end-of-stroke. Sensor 348 may be located adjacent to the pusher.In a preferred embodiment, sensor 348 is an electrical contact sensorthat senses the position of the pusher based on whether a component(e.g., nut 336) of the pusher has contacted the sensor. Sensor 348 mayinclude one or more contacting pins that are configured to contact oneor more contacting blades responsive to force applied on the contactingblades by the pusher. For example, the nut of the pusher may contact theblades at the end-of-stroke, causing the blades to move to contact thecontacting pins. The contacting pins may be coupled to the circuit boardvia a conductor (e.g., illustratively a spring) such that when the oneor more contacting pins contact the one or more contacting blades, acircuit is completed, which sends an electrical signal to controller360.

Skin detector 350 senses information indicative of whether the patchpump is touching skin. Controller 360 may cause the motor to run only ifskin detector 350 detects skin. Skin detector 350 preferably iselectrically coupled to controller 360 such that sensed signals are sentto controller 360 for processing and detecting whether the patch pump issecured to a pad, held by the wearer, or not touching skin. Skindetector 350 may be located on the skin-facing side of the patch pumpsuch that it detects whether the skin-facing side of the patch pump istouching skin. In some embodiments, skin detector 350 measurescapacitance.

Sensor 354 is configured to sense information indicative of thetemperature and humidity in the patch pump. Sensor 354 preferably iselectrically coupled to controller 360 such that sensed signals are sentto controller 360 for processing and detecting whether the temperatureand humidity are within respective predetermined ranges. If outside thepredetermined range(s), an alert may be generated using the vibrationmotor, the sound generator, and/or a communication sent to the softwareapplication.

In some embodiments, the pump may include a second skin detectionsensor. Similar to skin detector 350, skin detector 358 sensesinformation indicative of whether the patch pump is touching skin. Skindetector 358 preferably is electrically coupled to controller 360 suchthat sensed signals are sent to controller 360 for processing anddetecting whether the patch pump is secured to a pad, held by thewearer, or not touching skin. Skin detector 358 may be located on theopposite side of the patch pump such that is detects whether theopposite side of the patch pump is touching skin. In some embodiments,skin detector 358 measures capacitance. Controller 360 may cause themotor to run only if skin detector 350 detects skin and skin detector358 does not detect skin. If both skin detector 350 and skin detector358 detect skin, it may indicate that the wearer is holding the patchpump. In such a case, the patch pump should not deliver medication.

Sensor 374 is configured to sense information indicative of the wearer'sactivity level. Sensor 374 also may be configured to sense informationindicative of the location of the patch pump on the wearer's body.Sensor 374 preferably is electrically coupled to controller 360 suchthat sensed signals are sent to controller 360 for processing anddetecting the wearer's activity level. Sensor 374 may be anaccelerometer that measures the movement of the wearer.

Referring now to FIGS. 20A-20B, operation of the exemplary patch pump isdescribed, in which FIG. 20A corresponds to positions of the pumpcomponents when the cartridge is full of medication and FIG. 20Bcorresponds to positions of the pump components when the cartridge isempty. The pump motor may be disposed within the pump housing and may beconfigured to be coupled to a pusher and a cam (e.g., a circular cam)via a gearbox. Preferably, the pump motor is configured to move thepusher towards the cartridge to move the medication within the cartridgeinto an inflow needle within the cap. At the same time that the pusheris advancing, the cam disposed within the cap is configured to rotate todeliver a predetermined dose of medication to the cannula inserted intothe wearer's skin.

Pusher 335 may include screw 334, which may be coupled to gearbox 324and configured to rotate upon rotation of one or more gears with gearbox324. Nut 336 may be coupled to screw 334 such that rotation of screw 334causes nut 336 to move along screw 334. Nut 336 may be coupled to afirst end of bendable rod 338 and a second end of bendable rod 338 maybe coupled to cartridge contactor 340, which is configured to contactplunger 502 of cartridge 500. Upon rotation of screw 334 in a firstdirection, nut 336 is configured to move away from gearbox 324 such thatbendable rod 338 applies a force to cartridge contactor 340, causing atleast a portion of plunger 502 to move within cartridge 500. Uponrotation of screw 334 in a second direction, opposite the firstdirection, nut 336 is configured to move towards gearbox 324, such thatbendable rod 338 and cartridge contactor 340 move away from the cap ofcartridge 500. Bendable rod 338 may also be referred to as a curvedpiston.

In FIG. 20A, pusher 335 is depicted in a home position, when cartridge500 is full of medication. In the home position, nut 336 may be disposedadjacent to the location where screw 334 is coupled to the gearbox 324.In FIG. 20B, pusher 335 is depicted in a delivery position, aftercartridge 500 has delivered medication. Preferably, after all orsubstantially all of the medication within cartridge 500 has beendelivered, the battery of pump 300 should be recharged. Upon reaching apredetermined state in the charging cycle, pusher 335 is configured toreturn to the home position. For example, the controller, upon sensingthat the battery has reached the predetermined state (e.g., apredetermined time before full charge, such as 20 minutes), will causepump motor 328 to rewind thereby transitioning the pump back from theempty position of FIG. 20B to the full position of FIG. 20A. In someembodiments, the pump and the cap will not unlock until the battery issufficiently charged and the pump is in the home position. Gearbox 324preferably rotates screw 334 in the second direction such that cartridgecontactor moves away from plunger 502. Nut 336 may continue moving alongscrew 334 towards gearbox 324 until it reaches a contact sensor, asdescribed below. Upon sensing contact with nut 336, screw 334 isconfigured to reverse directions to rotate in the first direction suchthat nut 336 is advanced a short distance away from gearbox 324 and asmall space is created between nut 336 and the contact sensor. Resettingpusher 335 to the home position permits a new, pre-filled cartridge 500to be inserted into the patch pump.

Plunger 502 is a movable end of cartridge 500 and is configured to sealcartridge 500 such that medication does not leak from the cartridge.Plunger 502 preferably includes a flexible, elastomeric material that isable to deform when a substantial force is applied. Plunger 502 may beconfigured to flex based on the pressure within cartridge 500 such thatthe pressure is maintained within a predetermined range. Ensuring thepressure remains within the predetermined range helps ensure theaccuracy of each dose of medication, as described below. For example,plunger 502 may be configured to compress or deform when the pressurewithin cartridge 500 is over 800 or 1000 mbar. For example, plunger 502may be configured to advance into the cartridge a predetermined distancesuch as 3-4 um, preferably 3.7 um, after each push from pusher 335.Further, plunger 502 may include a first end that is configured tocontact pusher 335 and a second end that is configured to contact themedication within cartridge 500.

A risk with using an elastomeric plunger is the “stick-slip effect,”whereby the plunger does not move due to sticking until a force appliedto the first end exceeds a displacement needed for a dose of medication.Once the force overcomes the stick, the plunger may travel too far,resulting in an inaccurate dose. By pressurizing the cartridge prior todelivering microdoses, as described herein, the pump reduces thestick-slip effect by providing a counterforce via the pressurizedmedication on the pushing force caused by the pusher on the cartridge.As a result, the portion of the plunger of the cartridge contacting themedication does not move further than the distance needed to expel thedesired volume of medication of the microdose, thereby ensuring enhancedaccuracy of microdose volumes of medication. The counterforce from thepressurized medication also may cause the flexible plunger to compresswhile pumping a microdose. By advancing the piston a micro-step at eachdelivery of a dose via the microdosing system, pressure in the cartridgeis maintained. This pressure within the cartridge varies only minimallydue to stick-slip. Preferably, because the system is pressurized,stick-slip has minimal adverse effects on the volume of the microdoses.Advantageously, the patch pump may use this pressure to refill themicrodosing system with equivalent amounts of insulin for every deliverycycle.

For example, when the pressure within cartridge 500 is at a firstpressure, pusher 335 may be configured to cause the first end of plunger502 to move a first distance towards the cartridge cap and to deliver afirst dose of medication. Pusher 335 also may be configured to cause thesecond end of plunger 502 to move a third distance towards the cartridgecap. When the pressure within cartridge 500 increases to a secondpressure, pusher 335 may be configured to cause the first end of plunger502 to move a second distance towards the cartridge cap to deliver asecond dose of medication. Pusher 335 also may be configured to causethe second end of plunger 502 to move a fourth distance towards thecartridge cap.

Preferably, pusher 335 is configured to advance the same distance everytime screw 334 rotates. Plunger 502 may be configured so that each pushfrom pusher 335 causes the first end of plunger 502 to move the samedistance. Therefore, the first distance may be the same as the seconddistance. Plunger 502 further may be configured so that each push frompusher 335 causes the second end of plunger 502 to move a distance thatdepends upon the pressure within cartridge 500. For example, when thepressure within cartridge 500 increases, the distance that second end ofplunger 502 moves may decrease. Therefore, the third distance may begreater than the fourth distance. This adjustment by plunger 502 reducesthe risk that the pressure within cartridge 500 will move outside thepredetermined range of 600 mbar to 1000 mbar. Further, maintaining aconsistent pressure within the cartridge 500 reduces the risk thatvolume of each dose of medication falls outside the predetermined volumeof 0.08-1 uL, 0.2-0.6 uL, or 0.2 to 0.3 uL, preferably 0.25 uL±5%.Preferably, the volume of each dose of medication is within 5% of thevolume of the other doses delivered to the wearer.

The cap of patch pump preferably includes a microdosing systemconfigured to measure and deliver the predetermined doses of medication.Preferably, pusher 335, plunger 502, and the microdosing system worktogether to ensure the accuracy of the doses of medication. At the sametime that pusher 335 applies a force to plunger 502, the microdosingsystem is configured to rotate to deliver medication to the wearer. Themicrodosing system may include a lever system comprising one or morelevers configured to sequentially transition between a lowered position,wherein one or more levers contact a dosing tube such that medicationcannot flow through the dosing, and a raised position, wherein one ormore levers sequentially do not contact the dosing tube, such thatmedication is expelled from the dosing tube and to the wearer. The oneor more levers may act as valves that either permit or preventmedication from flowing through the dosing tube. Preferably, the leversystem is configured such that at least one lever is configured to be ina lowered position to close a portion of the dosing tube during theentire time the pump motor moves pusher 335.

With respect to FIG. 20C, an arrangement of wet and dry zones within thepatch pump is described. The patch pump may include isolated wet and dryzones to protect the electrical components from contacting any leakedmedication or other fluids. The patch pump may include dry zone 378 thatis configured to house the circuit board, motor, vibration motor, soundgenerator, battery, coil, gearbox, and one or more sensors. Dry zone 378may be encapsulated to exclude moisture from reaching the componentswithin the zone. Dry zone 378 may be encased in plastic and/or sealedvia welding. One or more dry zone vents 381 may be disposed on theplastic housing of dry zone 378 such that humidity and gas may escapethe housing and pressure may equilibrate. For example, dry zone vents381 may be made of Gore-Tex®. Dry zone 378 may be separated fromprotected wet zone 380 and unprotected wet zone 382 via one or moresealing members, for example, dry zone seals 379. Protected wet zone 380may be configured to house the pusher and unprotected wet zone 382 maybe configured to house the cartridge and the components of the capincluding the needles and microdosing system. In addition, cartridgeholder 332 may separate the protected wet zone from the dry zone and mayinclude one or more O-rings to seal off the zones when a cartridge isdisposed within the pump-cap assembly.

Referring now to FIG. 21A, further details of exemplary internalcomponents of the patch pump are described. Circuit board 314 preferablyis configured to have a flexible substrate that can bend and fold to fitto surround battery 318, gearbox 324, motor 328, and vibration motor 330within the pump housing. The components of circuit board 314 may bestrategically positioned in particular locations relative to thecorresponding components of the pump or cap. For example,photoplethysmography sensor 346 may be positioned on the skin-facingside of the pump patch so that photoplethysmography sensor 346 maydetect the wearer's heart rate or other physiologic parameters. Sensor320, which is configured to detect a parameter indicative of thepressure within cartridge 500, may be coupled to gearbox 324 and/or thepusher such that sensor 320 may detect the force applied to the pusher.Sensor 320 preferably is coupled to circuit board 314 via sensorconnector 321. Sensor 316, which is configured to detect an occlusion inthe dosing pathway, may be a hall-effect sensor. Preferably, sensor 316is disposed adjacent to microdosing system 410 such that sensor 316 candetect the position of a magnet of microdosing system 410 based onproximity of the magnet to the hall-effect sensor. Sensor 344, which isconfigured to determine the position of a cam plate of microdosingsystem 410, may be coupled to gearbox 324 and disposed adjacent tomicrodosing system 410 and magnet 396. Sensor 344 preferably is coupledto circuit board 314 via sensor connector 345.

Cartridge 500 is inserted into the patch pump such that the cartridgecap is disposed within the cap when the patch pump is locked. The longerthe distance the medication must travel through before delivering themedication to the wearer, the higher the risk that an occlusion willform within the needles. Preferably, cartridge 500 is positioned asclose as possible to microdosing system 410 and connection cavity 404such that the lengths of inflow needle 406 and outflow needle 408 are asshort as possible.

With respect to FIGS. 21B and 21C internal components of the pump-capassembly are shown with certain electrical components removed. FIG. 21Bdepicts the components within the gearbox. Motor 328, mechanicalcoupling 322, and screw 334 are coupled to the gearbox. One or more dryzone seals 379 may be disposed between the gearbox and mechanicalcoupling 322 and/or screw 334. Upon rotation of motor 328, the gearswithin the gearbox rotate, causing mechanical coupling 322 to rotate.Mechanical coupling 322 is coupled to a cam shaft of microdosing system410 such that rotation of mechanical coupling 322 causes the cam shaftto rotate, which in turn causes the lever system to deliver apredetermined dose of medication to the wearer. At the same time, thegears within the gearbox also cause screw 334 to rotate. Rotation ofscrew 334 causes nut 336 to move along screw 334, preferably in thedirection towards plunger 502 of cartridge 500.

FIG. 21C depicts another view of the system. Inflow needle 406 andoutflow needle 408 may be configured to have a short length in order toreduce the risk of occlusion. Inflow needle 406 preferably extends fromthe cartridge cap of cartridge 500, around connection cavity 404 and tomicrodosing system 410. Outflow needle 408 preferably extends frommicrodosing system 410 through connection cavity 404, and into thecannula inserted into the wearer's skin. Coupled between the inflow andoutflow needle is a dosing tube configured to hold the predetermineddose of medication.

Turning now to FIGS. 22A-22C, an exemplary contact sensor is described.The pump may include a sensor configured to detect the position of thepusher within the pump, which may indicate a state of the patch pump.The sensed position may be used to determine whether the pusher ispositioned within the pump such that a new, pre-filled cartridge may beinserted into the patch pump. The sensed position further may be used tomake sure that, when the pusher moves in the opposite direction toreturn to a home position, it does not stops moving before it reachesthe pump housing. The sensed position also may be used to determine thebattery level of the patch pump. As described below, until a sufficientbattery level is reached, the pump may remain locked to the cap,preventing replacement of the emptied cartridge.

In FIG. 22A, exemplary contact sensor 348, which may be an electricalcontact sensor, is disposed within the pump and configured to detect theposition of the pusher. For example, sensor 348 may include one or morecontacting pins that are configured to contact one or more contactingblades coupled to the pusher. The contacting pins may be coupled to thecircuit board via a conductor such that when the one or more contactingpins contact the one or more contacting blades, a circuit is completed,which indicates that the pusher is disposed in a starting position.

The pusher may include screw 334, nut 336 configured to move along screw334 such that bendable rod 338, which is coupled to nut 336, pushes acartridge contactor (not shown) to contact a plunger disposed within thecartridge. Upon movement of the pusher, the plunger is configured toadvance into the cartridge such that medication is moved towards theinflow needle of the cap. After the cartridge is empty, the pusher movesin an opposite direction, away from the cartridge and back to thestarting position. The position of the pusher may indicate that thepusher transitioned to a first position such that the cartridge ispermitted to be removed and exchanged for a subsequent cartridge.

One or more contacting blades 390 may be coupled to nut 336. Sensor 348preferably is disposed within pump housing 302 and adjacent tocontacting blades 390 of the pusher. For example, sensor 348 may includeone or more contacting pins 386 and 388 that are configured to contactcontacting blade 390 when the pusher is positioned near the pump housingback such that a new, pre-filled cartridge may be inserted into thepatch pump. Contacting pins 386 and 388 may be coupled to conductor 384,which is configured to electrically connect contacting pins 386 and 388to the circuit board. In FIG. 22B, the contact sensor in anon-contacting position, wherein contacting blades 390 are not connectedto contacting pins 386 and 388. In FIG. 22C, the contact sensor in acontacting position, wherein contacting blades 390 are connected tocontacting pins 386 and 388.

Sensor 348 may be electrically coupled to a controller such that sensedsignals are sent to the controller for processing and determining astate of the patch pump. For example, if sensor 348 detects that thepusher is in contact with contacting pins 386 and 388, the controllermay be configured to cause the pusher to move in an opposite directionto a home position, The controller further may be configured to monitorthe battery level of the patch pump and unlock the pump and cap if boththe battery level is at a sufficient level and sensor 348 senses contactwith the pusher.

Referring now to FIG. 23A, aspects of the gearbox of the pump aredescribed. Gearbox 324 is configured to cause simultaneous movement ofthe pusher and rotation of the microdosing system. One or more sensorsmay be disposed within gearbox 324 to determine the position of a camplate within the microdosing system or the pressure within thecartridge. For example, as described below, the position of the camplate may be used to validate that a dose of medication was properlydelivered to the wearer or may be used to ensure that pump and capremain locked together. Gearbox 324 may include a ferromagnetic bladethat may be coupled to the cam plate and, upon rotation, may generate anoscillation of a signal that can be used to count the teeth on theferromagnetic blade and accordingly whether the dosing cycle iscomplete. Gearbox 324 further may include a sensor that is configured tomeasure a force that is indicative of the pressure within the cartridge.

Referring now to FIG. 23B, an exemplary pressure sensor disposed withinthe pump is described. To ensure accurate doses of medication, the patchpump may be configured such that the pressure within the cartridge ismaintained within a predetermined range. For example, the predeterminedrange may be between 600 mbar and 1000 mbar. A sensor may be coupled toa pusher and configured to measure the force on the pusher, which may beindicative of the pressure within the cartridge.

For example, sensor 320 may include strain gauge 394 configured tomeasure deformation, for example, by measuring a change in electricalresistance. The pusher may include screw 334 having a first end, coupledto gearbox 324 and disposed adjacent to strain gauge 394, and a secondend, coupled to the cartridge. As the pressure within the cartridgeincreases, a greater force is applied to the pusher, and the pusherapplies the same force to gearbox 324 at force application point 392.The greater the force applied to the pusher, the greater the deformationof strain gauge 394. Sensor 320 preferably is operatively coupled to acontroller that may monitor the sensed pressure. The pressure within thecartridge must be increased until it falls within the predeterminedrange in order to ensure that the proper dose of medication is deliveredto the wearer. Further the controller may be configured to alert thewearer when the pressure falls outside the predetermined range. Forexample, a pressure under 600 mbar may indicate that a cartridge is notdisposed within the patch pump or that a cartridge was insertedincorrectly. A pressure over 1000 mbar may indicate that there is anocclusion within the cartridge cap, the inflow needle, and/or thecannula.

In a preferred embodiment, the patch pump is configured to be“initialized” prior to pumping medication from the cartridge past themicrodosing system and into the user. In this manner, the controller ofthe pump causes the pump to increase pressure within the cartridge intoa predetermined range prior to delivering the first dose of medicationfrom the cartridge to the wearer. By pressurizing the cartridge, thepatch pump ensures that precise volumes of microdoses of medication andare consistently and predictably provided to the user, including thefirst dose of medication from the cartridge. Further, the initializationensures that bubbles within the cartridge and the tubing connectedthereto are reduced and that the formation of bubbles is reduced.Advantageously, the patch pumps described herein may be generally“bubble free.”

With respect to FIG. 24A, a graph showing the relationship betweenpressure and volume is described, while FIGS. 24B and 24C show therelationship between the number of dosing cycles and the amount ofmedication delivered per cycle, without and with initialization. FIG.24D shows the accuracy of the patch pump with and without themicrodosing system and FIG. 24E shows a comparison of the percentageerror of flow for the patch pump described herein and other commerciallyavailable pumps. Accurate dosing requires that the pressure within thecartridge remains within a predetermined range. As further explainedbelow, the patch pump may include a microdosing system that isconfigured to measure and deliver a predetermined dose of medication.The microdosing system preferably includes a dosing tube with aflattened reservoir portion or compartment configured to hold apredetermined dose of medication. Because the reservoir portion isflexible, as the pressure of the medication increases, the reservoirportion expands more, allowing it to hold a greater volume ofmedication. Accordingly, pressure variations may result in delivery ofinconsistent and inaccurate doses of the medication. This relationshipis depicted in FIG. 24A. Preferably, the pressure within the cartridgeis between 600 mbar and 1000 mbar, and the ideal pressure is 800 mbar.When the pressure is at 800 mbar, the volume of medication is 0.25 ul,which is the preferred predetermined dose of medication.

As the pusher advances towards the plunger of the cartridge, moving theplunger into the cartridge, the pressure within the cartridge builds. Asthe pressure builds to 800 mbar, the expected volume of the medicationthat would be held within the dosing tube—if the levers allowedmedication to flow into the dosing tube—increases until it reaches thepreferred dose of 0.25 ul. Preferably, the microdosing system isconfigured to complete an initialization process such that delivery ofmedication to the wearer is prevented until the pressure within thecartridge reaches the predetermined range (e.g., 250 mbar to 2000 mbar,400 mbar to 1200 mbar, or 600 mbar to 900 mbar). If the microdosingsystem is configured to complete an initialization process such thatdelivery of medication to the wearer is prevented until the pressurewithin the cartridge reaches the predetermined range, the pressureincreases at a faster rate than if the there is no initialization of themicrodosing system.

FIG. 24B depicts what may occur if the microdosing system is configuredto deliver medication prior to initialization. The first dosing cyclewould deliver a first dose of medication having a much smaller volumethan the preferred volume of 0.25 ul. The second dosing cycle woulddeliver a second dose of medication having a larger volume than thefirst dose of medication, but the volume would still be less than thepreferred volume of 0.25 ul. As the dosing cycles continue, the pressurewould slowly increase to the predetermined range and the volume ofmedication delivered would slowly reach the predetermined volume.However, the first doses that the wearer would receive would be lessthan the predetermined dose of medication. Preferably, as in FIG. 24C,microdosing is disabled until the pressure is within 600 mbar and 1000mbar, such that the volume of each dose of medication is within 5% of0.25 ul. As the dosing cycles continue, the volume of each dose ofmedication should remain within 5% of the volume of the previous dose ofmedication.

Referring now to FIG. 24D, a graph showing the volume pumped per twomicrodoses over the total volume pump is described. Each data pointrepresents two microdoses, each microdose preferably 0.25 uL. Themeasurements for the patch pump without the microdosing system showsthat the system delivers accurate microdoses but with limited precision.In contrast, the measurements for the patch pump including themicrodosing system is both accurate and precise.

Referring now to FIG. 24E, a graph showing the percentage error of flowmeasurements for the patch pump with and without microdosing and thepercentage error of flow measurements for other commercially availablepumps is described. The percentage error of flow corresponds to theprecision of the pumps, a higher percentage error of flow indicatingthat the volume of each microdose has a greater variance and thus thepump is less precise. For each pump, the percentage error of flowdecreases with each delivery of a microdose. As shown in FIG. 24E, thepatch pump described herein (“Sigi”) is as precise or more precise thanother commercially available pumps.

Referring now to FIG. 24F, a schematic depiction of an exemplary pusherand microdosing system is described. Medication may be delivered fromcartridge 500, through inflow needle 406, and into flattened dosing tube447. Upon rotation of the microdosing system, the medication may then beforced out of flattened dosing tube 447, delivered through outflowneedle 408 to cannula 200, and inserted into the wearer. Preferably,microdosing system 410 and pusher 335 work together to maintain thepressure within cartridge 500 within a predetermined pressure range. Forexample, the strain of the plunger and the bendable rod of pusher 335within cartridge 500 at one end and the levers of microdosing system 410at the other end create a closed system in which the medication isdisposed, the closed system helping maintain the pressure within thepredetermined pressure range. The motor within the pump simultaneouslyadvances the plunger and activates microdosing system 410 at each dosingcycle. Preferably, the plunger advances in microsteps (e.g., 3-4 um,preferably 3.7 um) at each dosing cycle such that the pressure withincartridge 500 varies only minimally due to the “stick-slip”effect thatoccurs at the elastomeric portion of the plunger. The patch pump usesthe constant pressure to refill the reservoir of flattened dosing tube447 with equivalent volumes of medication at every dosing cycle. Inflowneedle 406, outflow needle 408, and dosing tube 447 are preferably madefrom materials compatible with insulin. For example, the inflow andoutflow needles may be made of stainless steel and dosing tube 447 maybe made of fluoropolymer tubing. Because the flow path for insulin maybe directly from cartridge 500 into inflow needle 406, then into dosingtube 447, then into outflow needle, then into cannula 200 (which is alsomade from insulin compatible material), all materials in contact withthe insulin are insulin compatible.

With respect to FIG. 25A, an exploded view an exemplary cap isdescribed. For example, cap 400 may include within cap housing 402 andinternal cap housing 401 the following components: cap clips 403,unclipping buttons 405, inflow needle 406, outflow needle 408,microdosing system 410, cam shaft 412, lever spring system 413, leversystem 414, cam plate 416, microdosing structure 418, spring 422, magnet428, tabs 430, flattened dosing tube 447, dosing tube support 454,and/or prongs 474. These components are described further herein.

Referring now to FIG. 25B, an exemplary microdosing system disposedwithin the cap, wherein an exemplary cam is in an initializationposition, is described. The cap is configured to deliver medication fromthe cartridge to the wearer and preferably includes microdosing system410 configured to measure and deliver the predetermined doses ofmedication. Preferably, microdosing system 410 is configured such thatthe insulin travels through a simple pathway designed for low shearstress, which avoids compromising the insulin. Microdosing system 410may be configured to only deliver the predetermined dose of medicationupon initialization of the microdosing system, when the pressure sensor,as described above, senses that the pressure within the cartridge iswithin the predetermined range. The initialization process helps ensurethat the microdosing system accurately measures the predetermined dosesof medication. The predetermined pressure range may depend upon thecartridge or medication used, but preferably is between 600 mbar and1000 mbar. When the pressure sensor senses that the pressure is withinthe predetermined range, the processor, may be configured to executeprogrammed instructions stored in the memory to cause the microdosingsystem to move from an initialization position to a dosing position,such that medication may be delivered to the wearer.

Microdosing system 410 is configured to provide for more accurate dosingand to reduce the noise from the delivery of the medication. Microdosingsystem 410 preferably is coupled to an inflow needle, which may extendfrom the cartridge to microdosing system 410, and an outflow needle,which may extend from microdosing system 410 to the cannula. Coupledbetween the inflow and outflow needle is a dosing tube configured toreceive the medication, the dosing tube having a flattened portionincluding a reservoir portion configured to hold the predetermined doseof medication. The reservoir portion may comprises one or more weldedportions that help ensure that a predetermined volume of medication isdelivered to the wearer.

Microdosing system 410 further may include a cam, which is configured torotate, and lever system 414, which is configured to contact the dosingtube and release the predetermined dose of medication into the outflowneedle upon interaction with the cam. The cam may be circular in shapeto reduce the overall size of the cam and/or to permit two microdoseswith a full 360 degree turn of the cam, although other shapes may besuitable. Lever system 414 may include one or more levers, each leverconfigured to be independently movable such that the movement of a firstlever does not affect the position of a second lever. The cam mayinclude cam shaft 412, which is oriented in a first plane, and cam plate416, which is coupled to cam shaft 412 and oriented in a second plane,the second plane preferably orthogonal to the first plane. The cam platemay be circular in shape to reduce the overall size of the cam plateand/or to permit two microdoses with a full 360 degree turn of the camplate, although other shapes may be suitable. Cam plate 416 may includea top surface having one or more raised surfaces that are configured tointeract with one or more levers of lever system 414 upon rotation ofcam shaft 412 such that the predetermined dose of medication isdelivered to the wearer. The raised surface(s) may extend away from thecircular portion of cam plate 416, such as in a direction generallyparallel to the longitudinal axis of the cam. Lever system 414 furthermay include magnet 428, which is configured to be used to detect anocclusion in the dosing pathway.

Microdosing system 410 further may include tabs 430, which areconfigured to rotate upon actuation by the motor. Tabs 430 preferablyare disposed at the end of cam shaft 412 such that tabs 430 may extendtowards and interact with the pump. Additionally, tabs 430 may beconfigured to function as a locking mechanism. For example, tabs 430 mayinteract with the mechanical coupling of the pump such that the capremains locked to the pump. The patch pump may be configured to remainlocked until the pusher of the pump is reset in a home position anduntil the battery is sufficiently charged.

Until a predetermined pressure range is detected within the cartridge,microdosing system 410 preferably remains in an initialization position,wherein cam plate 416 is disposed in a lowered position, as shown inFIG. 25B. In the initialization position, cam plate 416 is separate fromand not coupled to lever system 414 such that movement of cam plate 416does not cause movement of lever system 414. After the cap and the pumpare locked together, cam shaft 412 is configured to rotate in a firstdirection while the pusher is advanced into the cartridge, causing thepressure within the cartridge to increase.

Cam plate 416 may be configured to remain in the initialization positionuntil the pressure within the cartridge is within a predeterminedpressure range. To transition cam plate 416 to the dosing position, thedirection of rotation may be reversed to a second direction, opposite ofthe first direction. Cam plate 416 may have a lower portion disposedbelow the top surface of cam plate 416, the lower portion comprising anouter shaft that surrounds a lower shaft (e.g., cam shaft 412). One ormore wings may be disposed on the outer shaft such that wings 420 extendoutwards at a slight angle, similar to a thread. In the initializationposition, wings 420 interact with components of microdosing structure418 such that cam plate 416 is prevented from transitioning from thelowered, initialization position to a raised, dosing position to contactlever system 414. The components of microdosing structure 418 mayinclude spring 422, dampers 424, and mating surfaces 426. Spring 422 maybe disposed on the top surface of microdosing structure 418 and mayapply an upward force on cam plate 416. Dampers 424 may include aplastic material that is configured to minimize the noise from therotation of the circular cam. Dampers 424 also may act as a grippingmechanism on wings 420 when cam plate 416 transitions from theinitialization position to the dosing position. Mating surfaces 426 maybe configured to be positioned on microdosing structure 418 at a slightangle, similar to a thread, such that wings 420 may only transition tothe dosing position when cam plate 416 rotates in a particulardirection.

Referring now to FIGS. 25C-25F, further details of operation of thecircular cam is described. As the pressure within the cartridge isincreased to an optimal pressure, cam shaft 416 is rotated in a firstdirection, as depicted in FIG. 25C. Spring 422 applies an upwards forceon cam plate 416 such that wings 420 contact dampers 424 and matingsurfaces 426 but the circular cam remains in a non-gripping position.After the pressure is determined to be within the predetermined pressurerange, the direction of rotation of the circular cam is reversed to asecond direction, as depicted in FIG. 25D. The circular cam istransitioned to a gripping position wherein wings 420 are grippedbetween dampers 424 and mating surfaces 426. As cam plate 416 continuesto rotate and spring 422 continues to apply an upward force, wings 420slide upwards through mating surfaces 426, transitioning the circularcam to a sliding position, as depicted in FIG. 25E. Wings 420 continueto slide between dampers 424 and mating surfaces 426 until wings 420 aredisposed on top of microdosing structure 418. In the last step of theinitialization process, cam plate 416 shifts to the dosing position suchthat cam plate 416 contacts lever system 414, as depicted in FIG. 25F.The circular cam may be configured such that the transition from theinitialization position to the dosing position is permanent and, once inthe dosing position, the circular cam cannot return to theinitialization position.

In FIGS. 26A and 26B, the locations and functions of exemplary dampersand mating surfaces are described. Microdosing structure 418 may beconfigured to hold the circular cam in an initialization position untilthe pressure within the cartridge is within a predetermined range.Microdosing structure 418 may include dampers 424 and mating surfaces426, which are configured to interact with and grip the wings of the camplate when the circular cam transitions from the initialization positionto the dosing position. Mating surfaces 426 preferably are configured tohave an angled interface that functions as a thread when the wingsrotate upwards towards the lever system. Microdosing structure 418 alsomay be configured to minimize the noise from the rotation of thecircular cam. For example, dampers 424 may be made from a flexibleplastic material that is designed to minimize the sound from the contactbetween microdosing structure 418 and the top surface of cam plate 416.

Referring now to FIGS. 27A and 27B, details of a preferred microdosingsystem are described. Microdosing system 410 is configured to move apredetermined dose of medication towards an outflow needle and into thewearer's skin and may include a dosing tube, lever system 414 configuredto contact the dosing tube, and a circular cam configured to rotate. Thecircular cam preferably includes a cam shaft and cam plate 416, which,upon rotation of the cam shaft, is configured to interact with leversystem 414 and deliver the predetermined dose of medication towards thewearer. Lever system 414 may be coupled to lever spring system 413having one or more springs that are configured to keep the levers oflever system 414 in a lowered position. For example, microdosing system410 may include first lever spring 432 coupled to a first lever, middlelever spring 434 coupled to a middle lever, and second lever spring 436coupled to a second lever. Lever spring system 413 may be a singlestructure comprising one or more levers or may include separatestructures, each structure comprising a lever.

FIG. 27C depicts the microdosing system with the lever system spacedapart to reveal the dosing tube. The lever springs are configured toprovide a force on the lever system such that the levers of the leversystem maintain contact with the dosing tube and the pressure from thelevers prevents the medication from flowing through the dosing tubeuntil intended. The lever springs preferably are disposed abovecorresponding sections of flattened dosing tube 447, which is coupled todosing tube support 454. Flattened dosing tube 447 may include aflattened portion having three sections, dosing tube first portion 448,dosing tube reservoir portion 450, and dosing tube second portion 452.Preferably, dosing tube reservoir portion 450 is a compartment betweendosing tube first portion 448 and dosing tube second portion 452, thecompartment designed to hold a predetermined dose of medication. Forexample, first lever spring 432 may be disposed above dosing tube firstportion 448, middle lever spring 434 may be disposed above dosing tubereservoir portion 450, and second lever spring 436 may be disposed abovea dosing tube second portion 452.

With respect to FIG. 27D, further details of the microdosing system aredescribed. The lever system preferably includes first lever 442, middlelever 444, and second lever 446, which are configured to contact thedosing tube and act as valves to either permit or prevent medicationfrom flowing through the respective portion of the dosing tube. Firstlever 442 may be configured to be coupled to first lever spring 432 andto contact dosing tube first portion 448. Middle lever 444 may beconfigured to be coupled to middle lever spring 434 and to contactdosing tube reservoir portion 450. Second lever 446 may be configured tobe coupled to second lever spring 436 and to contact dosing tube secondportion 452.

Referring now to FIGS. 28A and 28B, details of the circular cam andlever system are described. Cam plate 416 is configured to interact withlever system 414 such that, upon rotation of cam plate 416, the leversof lever system 414 move in a series of steps and deliver apredetermined dose of medication to the wearer. Cam plate 416 mayinclude one or more rounded, raised surfaces that interact withcorresponding rounded lever ramps on the levers of lever system 414. Therounded surfaces ensure smooth movement between of the levers and mayhelp mitigate the sound of the microdosing system. Each time a levercontacts the raised surfaces of cam plate 416, the lever transitionsfrom a lowered position to a raised position, allowing medication toflow through the corresponding section of the dosing tube.

Cam plate 416 may include outer raised surfaces 438 and inner raisedsurfaces 440, positioned radially outward of outer raised surfaces 438.Outer raised surfaces 438 may be configured to contact the first leverramp of first lever 442 and the second lever ramp of second lever 446.Preferably, outer raised surfaces 438 are sized and shaped such that theouter raised surface may be disposed between the first lever ramp andthe second lever ramp without contacting either the first lever ramp orthe second lever ramp. Inner raised surfaces 440 may be configured tocontact only the middle lever ramp of middle lever 444. The raisedsurfaces on cam plate 416 may be configured such that a complete 360degree rotation of cam plate 416 delivers two predetermined doses ofmedication towards the wearer. For example, in FIG. 28A, cam plate 416includes two outer raised surfaces 438 and two inner raised surfaces440, the second outer and inner raised surfaces mirror images of thefirst outer and inner raised surfaces. As will be understood by one ofordinary skill in the art, cam plate 416 may include more than tworaised surfaces and may be configured such that a 360 degree rotation ora rotation of less than 180 degrees is required for delivery of apredetermined dose of medication.

Turning to FIGS. 29A-29C, operation of the lever system and exemplarydosing tube is described. The levers of lever system 414 are configuredto transition between a lowered position, such that the leverssequentially contact the dosing tube to prevent medication from flowingthrough the dosing tube, and a sequentially raised position, to expelmedication from the dosing tube to the wearer. Medication is deliveredfirst through inflow needle 406, which is configured to extend from thecartridge to a first end of the dosing tube, next though the dosingtube, and then through outflow needle 408, which is configured to extendfrom a second end of the dosing tube to the cannula inserted into thewearer. The first end of the dosing tube is adjacent to first lever 442and dosing tube first portion 448. The second end of the dosing tube isadjacent to second lever 446 and dosing tube second portion 452. Inflowneedle 406 and outflow needle 408 preferably are coupled to the dosingtube such that the needles are disposed within the dosing tube, as shownin FIG. 29B. For example, the outer diameter of inflow needle 406 andoutflow needle 408 may be the same as or substantially similar to theinner diameter of the first and second ends of the dosing tube.

FIG. 29C depicts a close up of the levers and dosing tube. The dosingtube preferably is disposed on dosing tube support 454, which isconfigured to provide a support for the dosing tube, which includes aflattened portion having three sections. Dosing tube first portion 448is a first end of the flattened portion and may be disposed adjacent tofirst lever 442 such that, when first lever 442 is in a loweredposition, medication is prevented from flowing from inflow needle 406through dosing tube first portion 448. Dosing tube second portion 452 isa second end of the flattened portion and may be disposed adjacent tosecond lever 446 such that, when second lever 446 is in a loweredposition, medication is prevented from flowing through dosing tubesecond portion 452 and into outflow needle 408. Dosing tube reservoirportion 450 is the middle portion that is substantially surrounded byone or more welded portions. Dosing tube reservoir portion 450 may bedisposed adjacent to middle lever 444 such that, when middle lever 444is lowered and second lever 446 is raised, medication is expelled fromdosing tube reservoir portion 450 through dosing tube second portion452.

Preferably, the levers are sized and shaped to correspond with the sizeand shape of the dosing tube portions. For example, first lever 442 andsecond lever 446 may contact only a small section of the flattenedportion of the dosing tube. Middle lever 444 may contact a large sectionof the flattened portion of the dosing tube and may be sized and shapedsuch that, when middle lever 444 transitions from a raised position to alowered position, substantially all the medication held within dosingtube reservoir portion 450 is expelled towards the wearer.

Referring now to FIG. 29D, further details of the microdosing system,are described. In FIG. 29D, the lever system and lever springs areremoved to reveal how the inflow and outflow needles are disposed withinthe pump housing. Inflow needle 406 preferably extends from thecartridge to the first end of the dosing tube. Inflow needle 406 may beconfigured to contact microdosing structure 418 and extend aroundconnection cavity 404 of the cap housing. Outflow needle 408 preferablyextends from the second end of the dosing tube, through connectioncavity 404, and into the cannula inserted into the wearer's skin.

Turning to FIGS. 30A-K, operation of microdosing system is described inan exemplary series of steps to deliver a predetermined dose ofmedication to the wearer. A predetermined dose of medication may bedelivered upon rotation of the circular cam, which is configured tointeract with the lever system. First lever 442 may include a firstextended arm having first lever ramp 456 that is configured to contactthe outer raised surfaces of cam plate 416, middle lever 444 may includea middle extended arm having middle lever ramp 458 that is configured tocontact the inner raised surfaces of cam plate 416, and second lever 446may include a second extended arm having second lever ramp 460 that isconfigured to contact the outer raised surfaces of cam plate 416. Eachextended arm may extend from the lever ramps to the dosing tube.Preferably, the lever ramps are configured to maintain smooth andcontinuous contact with the raised surfaces of cam plate 416 such thatthe noise from rotation of the circular cam is minimized. For example,the lever ramps may have a rounded shape and the raised surfaces mayhave a corresponding rounded shape.

FIGS. 30A and 30B show the microdosing system in a first position,wherein first lever 442, middle lever 444, and second lever 446 are in alowered position such that the levers are pressing down on thecorresponding portions of the dosing tube and medication cannot flowpast any of the levers. In the first position, none of the lever rampscontact the raised surfaces of the cam plate.

FIGS. 30C and 30D show the microdosing system in a second position. Uponrotation of the cam plate, outer raised surface 438 contacts first leverramp 456, moving first lever 442 from a lowered position to a raisedposition. Middle lever 444 and second lever 446 remain in a loweredposition such that medication can flow through dosing tube first portion448 but cannot flow past dosing tube reservoir portion 450.

FIGS. 30E and 30F show the microdosing system in a third position. Uponfurther rotation of the cam plate, outer raised surface 438 remains incontact with first lever ramp 456 such that first lever 442 remains in araised position and inner raised surface 440 contacts middle lever ramp458, moving middle lever 444 from a lowered position to a raisedposition. Second lever 446 remains in a lowered position such thatmedication can flow through dosing tube first portion 448 and intodosing tube reservoir portion 450 but cannot flow past dosing tubesecond portion 452. In the third position, dosing tube reservoir portion450 is configured to fill and expand with the predetermined dose ofmedication.

FIGS. 30G and 30H show the microdosing system in a fourth position. Uponfurther rotation of the cam plate, outer raised surface 438 moves to aposition between first lever ramp 456 and second lever ramp 460 suchthat outer raised surface 438 is not in contact with either first leverramp 456 or second lever ramp 460. Inner raised surface 440 remains incontact with middle lever ramp 458 such that middle lever 444 remains ina raised position. First lever 442 moves from a raised position to alowered position and second lever 446 remains in a lowered position suchthat the predetermined dose of medication is held within dosing tubereservoir portion 450 and is unable to flow past dosing tube secondportion 452.

FIGS. 301 and 30J show the microdosing system in a fifth position. Uponfurther rotation of the cam plate, outer raised surface 438 contactssecond lever ramp 460, moving second lever 446 from a lowered positionto a raised position, and inner raised surface 440 remains in contactwith middle lever ramp 458 such that middle lever 444 remains in araised position. First lever 446 remains in a lowered position such thatmedication can flow through dosing tube second portion 452 to outflowneedle 408, but cannot flow back through dosing tube first portion 448.

FIGS. 30K and 30L show the microdosing system in a sixth position. Uponfurther rotation of the cam plate, outer raised surface 438 remains incontact with second lever ramp 460 such that second lever 446 remains ina raised position and inner raised surface 440 moves to a position pastmiddle lever ramp 456 such that middle lever 444 moves from a raisedposition to a lowered position such that middle lever 444 appliespressure to dosing tube reservoir portion 450, forcing the predetermineddose of medication past dosing tube second portion 452 and into outflowneedle 408. This step ensures the accuracy of the medication deliveryand that all of the predetermined dose of medication is delivered to thewearer such that no medication remains in dosing tube reservoir portion450.

FIG. 31 provides a schematic depiction of the series of steps configuredto deliver the predetermined dose of medication to the wearer. Asdescribed with respect to FIGS. 30A-L above, the lever system includeslever ramps, which are configured to move the levers between a loweredposition and a raised position upon contact with raised surfaces on thecam plate. Each lever is configured to contact a different portion ofthe dosing tube. Preferably, first lever 442 contacts dosing tube firstportion 448, middle lever 444 contacts dosing tube reservoir portion450, and second lever 446 contacts dosing tube second portion 452.

The steps depicted in FIG. 31 correspond with the steps shown in FIGS.30A-L. In the first position, first lever 442, middle lever 444, andsecond lever 446 are in a lowered position and contact the correspondingportions of the dosing tube such that the medication cannot flow throughthe dosing tube or past any of the levers. In the second position, firstlever 442 moves to a raised position and middle lever 444 and secondlever 446 remain in a lowered position such that medication may onlyflow through dosing tube first portion 448. In the third position, firstlever 442 remains in a raised position, middle lever 444 moves to araised position, and second lever 446 remains in a lowered position suchthat medication may flow into dosing tube reservoir portion 450, but notpast second lever 446. In the fourth position, first lever 442 moves toa lowered position, middle lever 444 remains in a raised position, andsecond lever 446 remains in a lowered position such that thepredetermined dose of medication is measured within dosing tubereservoir portion 450 and cannot flow past either first lever 442 orsecond lever 446. In the fifth position, first lever 442 remains in alowered position, middle lever 444 remains in a raised position, andsecond lever 446 moves to a raised position such that predetermined doseof medication may flow from dosing tube reservoir portion 450 andthrough dosing tube second portion 452. In the sixth position, firstlever 442 remains in a lowered position, middle lever 444 moves to alowered position, and second lever 446 remains in a raised position suchthat the all of the predetermined dose of medication is forced out ofdosing tube reservoir portion 450 and through dosing tube second portion452 towards the wearer. Following this step, the microdosing systemreturns to the first position wherein all of the levers are in a loweredposition.

Referring now to FIGS. 32A and 32B, an exemplary system for detecting anocclusion in the dosing pathway, from cartridge 500 to the locationmedication is delivered within the skin of the wearer, is described. Anocclusion in the dosing pathway may occur within the dosing tube, withinoutflow needle 408, or within the cannula. Fast detection of an infusionanomaly (e.g., an occlusion) in the dosing pathway allows themicrodosing system to monitor the accuracy of the microdosing system andmitigates the risk that the wearer fails to receive a proper dose ofmedication. Pump 300 may include sensor 316, which may be configured toconfirm the accuracy of the microdosing system and that thepredetermined dose of medication was delivered to the wearer. Sensor 316preferably is configured to sense displacement of one or more levers,which may be indicative of whether there is an occlusion disposed withinthe dosing tube, within outflow needle 408, or within the cannula.Sensor 316 may be electrically coupled to a controller such that sensedsignals are sent to the controller for processing and detecting anocclusion. The controller may sense an occlusion if the senseddisplacement is outside a threshold range, the determination based onthe proximity of the magnet to the hall-effect sensor over time. Forexample, the controller may be configured to monitor whether themeasured Hall-effect sensor values are within predetermined Hall-effectsensor value ranges that are expected for each step of the dosing cycleor if the measured Hall-effect sensor values change at a time it shouldremain the same. The controller may determine there is an occlusionbased on one or more sensed signals. For example, detection of anocclusion may be based on sensed signals over more than one dosingcycles.

Sensor 316 may also be used to determine whether the microdosing systemis in the initialization position. For example, the controller may sensethat the microdosing system is in the initialization position if thesensor does not sense any displacement of the one or more levers over apredetermined period of time. Further, sensor 316 may be used todetermine whether the cap is coupled to the pump. The controller mayconfirm that the cap and pump are properly coupled together if sensor316 senses that the one or more levers is disposed in a predeterminedposition. Alternatively or additionally, information sensed by sensor316 may be used to determine a status of the cap, for example, whetherthe cap is “new” or “used.” For example, the when the cam plate movesfrom the initialization position to the dosing position, the magnetcoupled to the lever system may move slightly towards the pump.Information from sensor 316 may be used to determine that themicrodosing system has completed the initialization process andtherefore the cap is “used.” Information sensed by sensor 316 may beused to determine if the cap is coupled to the pump. For example, if amagnetic field is not sensed by sensor 316, the controller indicatesthat the cap is not coupled to the pump because the magnet in the cap isnot being sensed. As such, the controller will not activate pumpinguntil the cap is coupled to the pump. Further, the position of themagnet within the cap, as sensed by sensor 316 based on the strength ofthe magnetic field, may indicate the status of the cap. For example, ifthe magnetic field is within a predetermined range, the controller willindicate that the cap is in the initialization position. If the magneticfield is within a second predetermined range, the controller willindicate that the cap is in the dosing position. In some embodiments,the strength of the magnetic field is weaker when the cap is in theinitialization position because the magnet is further from the pump. Asthe cap moves from the initialization position to the dosing position,the magnet is moved closer to the cap, thereby increasing the strengthof the sensed magnetic field. As such, the second predetermined rangemay be higher than the first predetermined range to indicate that thepump is in the dosing position, as determined by the controller.

FIGS. 32A and 32B show a simplified view of the microdosing system intwo positions. Disposed within pump 300 is sensor 316 and cartridge 500,which may be coupled to inflow needle 406. Inflow needle 406 may becoupled to the dosing tube and the dosing tube may be coupled to outflowneedle 408. The lever system may include middle lever spring 434, whichmay apply a force on middle lever 444 such that middle lever 444 remainsin a lowered position adjacent to dosing reservoir portion 450. At theopposite end of middle lever 444, magnet 428 may be disposed. Magnet 428may be positioned such that when middle lever 444 moves from a loweredposition to a raised position, in FIG. 32B, magnet 428 moves closer tosensor 316. Sensor 316 preferably is a Hall-effect sensor that isconfigured to detect a magnetic field of a magnet disposed on the leversystem.

In FIG. 32A, the dosing tube reservoir portion 450 is in a compressedstate, such that no medication is disposed within dosing tube reservoirportion 450. In the compressed state, middle lever 444 is positioned ina lowered position such that magnet 428 is disposed farther away fromsensor 316. The farther magnet 428 is away from sensor 316, the smallerthe Hall-effect value will be. In FIG. 32B, when dosing tube reservoirportion 450 is in an expanded state, medication is disposed withindosing tube reservoir portion 450. In the expanded state, middle lever44 is positioned in a raised position such that magnet 428 is disposedcloser to sensor 316 such that the Hall-effect value is greater than theHall-effect value when dosing tube reservoir portion 450 is in thecompressed state.

Referring now to FIG. 32C, the changing position of the magnet disposedon the middle lever of the microdosing system during a dosing cycle isdescribed. In the first step, first lever 442 and middle lever 444 arein a raised position such that medication may flow into dosing tubereservoir portion 450. After first lever 442 moves to a loweredposition, second lever 446 moves to a raised position. A portion of themedication within dosing tube reservoir portion may flow into theoutflow needle and thus middle lever 444 and magnet 428 may move aslightly farther away from the pump and sensor. In the third step,middle lever 444 moves to a lowered position such that a force isapplied to dosing tube reservoir portion 450. If there are no occlusionswithin the dosing tube or within the outflow needle or cannula, theremaining medication disposed within dosing tube reservoir portion 450is forced into the outflow needle and middle lever 444 and magnet 428move to a lowered position. In the last step, middle lever 444 andmagnet 428 move to the farthest position away from the pump and sensor.

FIGS. 33A and 33B provide schematic depictions of the series of stepsconfigured to deliver the predetermined dose of medication to thewearer, wherein the dosing pathway is not occluded and the dosingpathway is occluded, are illustrated. FIG. 33A is similar to FIG. 30 ,described above, and also includes arrows A and B pointing to two stepsof the microdosing process. Arrow A is pointing to the sixth position ofthe microdosing system wherein middle lever 444 is configured to havemoved from a raised position to a lowered position, thus forcing thepredetermined dose of medication towards the wearer. Arrow B is pointingto the second position of the microdosing system wherein, first lever442 is configured to have moved from a lowered position to a raisedposition, thus permitting medication to flow through dosing tube firstportion 448 into dosing tube reservoir portion 450.

While FIG. 33A depicts proper operation of the microdosing system, FIG.33B depicts a scenario in which there is an occlusion in the dosingpathway. For example, the block may be disposed near dosing tube secondportion 452 and outflow needle 408 such that medication can flow througha portion of the dosing tube but cannot reach the wearer. In anotherexample, the block may be disposed within the cannula. In FIG. 33B,arrow A is pointing to the sixth step, wherein middle lever 444 isconfigured to have moved to a lowered position such that predetermineddose of medication flows towards the wearer. However, dosing tube secondportion 452 is blocked due to an occlusion in the dosing pathway,preventing the medication from flowing out of dosing tube reservoirportion 450 such that middle lever 444 is unable to move to a loweredposition. In the next step, wherein the predetermined dose should becompletely delivered to the wearer, second lever 446 is able to move toa lowered position, but the block prevents any delivery of medication.At arrow B, when the next dosing cycle starts, first lever 442 isconfigured to move to a raised position and middle lever 444 and secondlever 446 are configured to remain in a lowered position. However,because the predetermined dose of medication was unable to move intooutflow tube 408, middle lever 444 is finally able to move to thelowered position, pushing the predetermined dose of medication back intothe inflow tube.

FIGS. 33C and 33D illustrate the position of the magnet disposed on themiddle lever of the microdosing system, wherein the dosing pathway isnot occluded and wherein the dosing pathway is occluded. In FIG. 33C,magnet 428 changes positions when the medication is delivered to theoutflow needle. In FIG. 33D, because there is an occlusion in the dosingpathway, for example, within the dosing tube, within the outflow needle,or within the cannula, middle lever 444 is not able to move to thelowered position and thus magnet 428 does not significantly changepositions. By monitoring the value of a parameter(s) (e.g., theHall-effect value), the sensor is able to determine the position ofmagnet 428 and middle lever 444, these values indicating whether thereis an occlusion in the dosing pathway. For example, if the magnet doesnot move at least a predetermined distance relative to the pump (e.g.,away from the pump) during each microdosing cycle, the controller isable to determine an occlusion in the fluid flow path. In FIG. 33D, themagnet does not move at least the predetermined distance away from thepump during a microdosing cycle, thereby indicating an occlusion. Assuch, the patch pump ensures real-time monitoring of each micro-dosingcycle resulting in ultrafast occlusion detection.

Referring now to FIG. 34 , a graph showing Hall-effect sensor valuesover time when the dosing pathway is not occluded and when the dosingpathway is occluded is illustrated, and corresponds to the twosituations presented in FIGS. 33A and 33B. At point A, in a non-occludedsystem, the middle lever would move to a lowered position such that thepredetermined dose of medication was forced out of the dosing tubereservoir portion. When the middle lever moves to a lowered position,the magnet disposed at the end of the middle lever moves farther awayfrom the hall-effect sensor and therefore the Hall-effect sensor valuedecreases. However, if there is a blockage within the dosing tube secondportion, the outflow needle, or the cannula, middle lever would not beable to move to a lowered position and the position of the magnet wouldnot either. The Hall-effect sensor value therefore would remainsubstantially the same.

At point B, in a non-occluded system, the middle lever would haveremained in a lowered position while the dosing cycle was beginningagain. However, if the predetermined dose of medication was unable todeliver the medication from the dosing tube reservoir portion, themiddle lever would have started in a raised position. As the first leveris moved to a raised position, the middle lever is able to move to thelowered position, forcing medication within the dosing tube reservoirportion to flow back into the inflow tube. Therefore, in an occludedsystem, at point B, the magnet disposed at the end of the middle levermoves farther away from the Hall-effect sensor such that the Hall-effectsensor value decreases.

A controller may be operatively coupled to the sensor and may beconfigured to determine whether there is an occlusion in the dosingpathway. For example, the controller may be configured to monitorwhether the measured Hall-effect sensor values are within predeterminedHall-effect sensor value ranges that are expected for each step of thedosing cycle or if the measured Hall-effect sensor values change at atime it should remain the same. If there is an occlusion, at point A,the measured Hall-effect sensor value may exceed the predeterminedHall-effect sensor value range for that step. At point B, the measuredHall-effect sensor value decreases while the predetermined Hall-effectsensor value remains the same. The controller may determine there is anocclusion based off of the measurements at point A, point B, or bothpoint A and point B.

Referring now to FIGS. 35A-35D, an exemplary system configured todetermine the position of the circular cam is described, wherein FIG.35E is a graph showing signal strength over time as the circular camrotates. Another way to validate that the predetermined doses ofmedication are properly delivered to the wearer and to ensure that thedosing cycle is fully completed is by determining the position of thecam plate. Monitoring of the position of the cam plate also helps thecontroller determine the absolute stopping position for each dosingcycle such that the controller can ensure that the patch pump remainslocked, as described above. For example, a ferromagnetic blade havingteeth may be coupled to the cam plate and, upon rotation, may generatean oscillation of a signal that can be used to count the teeth on theferromagnetic blade. The generated oscillations may be used as anincremental sensor to determine the position of a cam plate andaccordingly whether the dosing cycle is complete.

Preferably, pump 300 includes circuit board 314 having sensor 344disposed on one side of circuit board 314 and magnet 396 disposed on theother side of circuit board 314 and adjacent to sensor 344. Pump 300further may include gearbox 324 having ferromagnetic blade 323.Ferromagnetic blade 323 may have a plurality of teeth and the pluralityof teeth may include one or more gaps 325. Gaps 325 may be spacedequally around ferromagnetic blade 323 and preferably align with the endof a dosing cycle. For example, one 360 degree rotation of cam plate 416may complete two doses cycles. Ferromagnetic blade 323 may include twogaps 325 disposed opposite of each other and configured to align withthe end of a dosing cycle.

Sensor 344 preferably is electrically coupled to a controller such thatsensed signals are sent to the controller for determining the positionof cam plate 416. Gaps 325 may create longer (dT1>dT2) and stronger(A1>A2) oscillations, as shown in FIG. 35E. By monitoring theoscillations, and determining the position of cam plate 416, thecontroller is able to determine the absolute stopping position for eachdosing cycle. This determination also may help the controller ensurethat the patch pump remains locked, as described above.

With respect to FIGS. 36A and 36B, an exemplary tube flattening systembefore and after the dosing tube is flattened is described. The dosingtube preferably is made from a flexible polymer such that the levers ofthe lever system may apply pressure to the dosing tube, causing thedosing tube to deflect and prevent the medication from flowing throughthe dosing tube. The dosing tube preferably includes dosing tubereservoir portion 450, which is designed to slightly expand such thatthe predetermined dose of medication is accurately measured. Bymonitoring the pressure within the cartridge and by measuring thepredetermined dose of medication by volume, the accuracy of the dose isincreased. Dosing tube reservoir portion 450 also may include weldedportions that are configured to increase the accuracy of the volumewithin the reservoir.

Tube flattening system 800 is configured to flatten dosing tubereservoir portion 450. Tube flattening system 800 provides advantagesover the methods of the prior art wherein the tube is blow molded andthen flattened. One of the key benefits of this system is that itreduces the risk that the tubing walls within dosing tube reservoirportion 450 do not have a constant thickness and rigidity. Uniformityalong the tubing walls helps ensure that each manufactured dosing tubereservoir portion 450 expands to the same size, thus ensuring that thepredetermined doses of medication are similar among different devices.

Tube flattening system 800 may include two or more raised portions 802that are spaced apart such that unflattened dosing tube 466 may fitbetween a first and second raised portion without significant excessspace remaining. Tube flattening system 800 further may include press806, which is configured to apply pressure onto unflattened dosing tube466 to create a flattened dosing tube including dosing tube reservoirportion 450, which is designed to hold a predetermined dose ofmedication. Preferably, press 806 moves from a raised position such thatpress 806 does not contact unflattened dosing tube 466 to a loweredposition such that press 806 presses on unflattened dosing tube 466until it reaches thickness guide 804. Thickness guide 804 preferably isdisposed on either side of unflattened dosing tube 466 and protrudesabove lower portion 808 of tube flattening system 800 to a height thatis substantially the same as the preferred thickness of dosing tubereservoir portion 450.

Turning to FIG. 37 , an exemplary welded dosing tube is described. Tofurther ensure that the predetermined dose of the medication isaccurate, dosing tube reservoir portion 450 may include welded portions468, which help define a specific volume to be filled with medication.Welded portions 468 also may increase the efficiency of thewatertightness such that the levers can provide less pressure on thedosing tube while still preventing the medication from flowing towardsthe wearer. Welded portions 468 may be disposed on the outer portions ofdosing tube reservoir portion 450 such that the medication may stillflow through the dosing tube. Preferably, the dosing tube is welded ontodosing tube support 454 via laser welding. The dosing tube may betransparent to a laser and dosing tube support 454 may not betransparent to the laser. Dosing tube support 454 is configured toprovide a support for the dosing tube during welding and also isconfigured to help position the dosing tube within the patch pump duringassembly.

Referring now to FIGS. 38A-38C, exemplary mechanisms for locking thepatch pump to the pad are described. The locking mechanisms preferablyare configured such that the cap remains secured to the pump and thepatch pump remains secured to the pad throughout the wearer's dailymotions. In FIG. 38A, the pump-cap assembly when the pump are lockedtogether. The patch pump may include a pump having pump housing 302 anda cap having cap housing 402 and may be configured to house cartridge500. Cap housing 402 may include cap lock 470 and pump housing 302 mayinclude pump housing lock 398, configured to interact with cap lock 470.The cap may be configured to couple to the pump via a twisting motion.For example, the cap may be placed onto the pump in a first positionsuch that the inflow needle of the cap pierces the cartridge cap ofcartridge 500. The cap may then be rotated until cap lock 470 couples topump housing lock 398.

In FIG. 38B the pump-cap assembly and pad are locked together. In orderto ensure that cartridge 500 remains within the patch pump and that theoperation of the patch pump is not interrupted by the wearer, the patchpump is configured to couple to the pad such that the pump and capcannot be uncoupled from each other until the patch pump is uncoupledfrom the pad. For example, cap housing 402 further may include padinterface 472 at a different edge of cap housing 402. Cap lock 470 andpad interface 472 may be configured to interact with correspondingfeatures of pad skeleton 104. Once the patch pump is secured to the pad,the interaction between pad skeleton 104, cap lock 470 and pump housinglock 398 ensure that the patch pump cannot be opened when disposed onthe skin of the wearer.

In FIG. 38C, distortion that may occur if the pump-cap assembly and padare not locked together is described. In particular, if the patch pumpis not properly coupled to the pad, cap housing 402 may deform, causingthe cap to uncouple from the pump. This unlocking could cause seriousconsequences for the wearer, and thus must be prevented. One way toprevent the unlocking is to lock the patch pump to the pad, as in FIG.38B.

Referring now to FIGS. 39A-39F, exemplary mechanisms for locking the capto the pump are described. In addition to the locking mechanisms notedabove, the cap and pump further may include a rotational lockingmechanism disposed between pump housing 302 and cap housing 402. Thislocking mechanism ensures that the wearer cannot uncouple the cap fromthe pump during delivery of medication. In FIGS. 39A and 39B, the capmay be placed onto the pump in an open, unlocked position such that theinflow needle of the cap pierces the cartridge cap of cartridge 500. Thepump may include tabs 430, which are coupled to the microdosing system,and the cap may include mechanical coupling 322, which is coupled to thegearbox. Both tabs 430 and mechanical coupling 322 are configured torotate upon actuation of the gearbox. Preferably, in the closedposition, tabs 430 are configured to be disposed within mechanicalcoupling 322 such that rotation of mechanical coupling 322 causesrotation of tabs 430, which causes rotation of the circular camdescribed above. In the unlocked position, tabs 430 and mechanicalcoupling 322 may be disposed in a vertical position, perpendicular tothe skin-facing side of the patch pump.

After the inflow needle of the cap is disposed within cartridge 500, thecap then may be rotated until the cap couples to the pump such that thepump and cap are in a closed, but unlocked position, as in FIG. 39C.Tabs 430 are configured to protrude from cap housing 402 such that tabs430 must be in the vertical position in order to either couple oruncouple the cap from the pump. For example, tabs 430 may be configuredto move through channel 303 of pump housing 302. Preferably, channel 303is sufficiently narrow such that tabs 430 cannot travel through channel303 when tabs 430 are in a horizontal position. After the cap is coupledto the pump, the controller may be configured to rotate mechanicalcoupling 322 such that mechanical coupling 322 and tabs 430 are in alocked position, as in FIG. 39D. In FIGS. 39E and 39F, tabs 430 are inan unlocked position and a locked position, respectively.

A microdosing system is disposed within the cap and is configured tomeasure and deliver a predetermined dose of medication. The microdosingsystem may include a dosing tube, circular cam, configured to rotate,and a lever system, configured to contact the dosing tube and releasethe predetermined dose of medication into an outflow needle. Thecircular cam may include a cam shaft and a cam plate coupled to the camshaft. Preferably, the cam plate includes a top surface having one ormore raised surfaces configured to interact with one or more levers ofthe lever system upon rotation of the cam shaft. Tabs 430 may bedisposed at the end of the cam shaft such that tabs 430 may extendtowards and interact with the pump. When the motor interacts with thegearbox, it causes both the pusher to move towards the plunger of thecartridge and mechanical coupling 322 to rotate, causing rotation oftabs 430, which causes the microdosing system to deliver medication tothe wearer. Preferably, a 180 degree rotation of mechanical coupling 322delivers one dose of medication.

Each dosing cycle may occur within a predetermined time period (e.g.,0.5 seconds) such that mechanical coupling 322 and tabs 430 are in thevertical position for a very limited amount of time such that the riskthat the wearer may uncouple the cap and pump is reduced. In a preferredembodiment, tabs 430 are permitted to travel through channel 303 in arange of +−10 degrees from the vertical position. Upon each rotation ofmechanical coupling 322 and tabs 430, it may be possible to open the captwice, each time for about 5 hundredths of a second. However, it may notbe possible to open the cap when the pump-cap assembly is clipped to thepad because the cap lock secures the pump-cap assembly to the pad.Preferably, when the pump-cap assembly is not clipped to the pad, theskin detector does not detect the skin and the controller stops the pumpsuch that mechanical coupling 322 and tabs 430 are disposed in a lockedposition and the wearer cannot unlock the pump-cap assembly.

The patch pump may be configured to remain locked even after cartridge500 is empty. Preferably, mechanical coupling 322 and tabs 430 remain ina locked position until the pusher of the pump is reset to the homeposition and until the battery is sufficiently charged. The controllermay be configured to monitor the battery level of the patch pump andunlock the pump and cap if both the battery level is at a sufficientlevel and a sensor senses that the contacting blade of the pusher is incontact with the contacting pins.

Referring now to FIGS. 40A and 40B, exemplary locking protrusionsdisposed on the cap and locking receptacles on the pump are described.Surrounding the cartridge, the cap may include one or more lockingprotrusions and the pump may include one or more corresponding lockingreceptacles configured to receive the locking protrusions. The lockingprotrusions and receptacles are configured to lock the cap to the pumpsuch that the continuous force that the pusher places onto the cartridgedoes not uncouple the cap from the pump. Because the cartridge mustremain pressurized in order to ensure accurate dosing, the cartridge mayapply a considerable amount of force on the cap.

Cap 400 may include one or more locking protrusions 476 configured tosurround the region of cap 400 where inflow needle 406 pierces thecartridge cap of cartridge 500. Pump 300 preferably includes one or morecorresponding locking receptacles 399, each locking receptacle 399configured to engage a locking protrusion 476. Locking protrusions 476and locking receptacles 399 may be radially spaced surrounding theinflow needle, may be various sizes and shapes, and may be configured tolock to each other upon rotation of the cap from an open position to aclosed position. Preferably, cap 400 includes at least three lockingprotrusions 476 and pump 300 includes at least three correspondinglocking receptacles such that torque is minimized. Locking protrusions476 may be configured to prevent the cap from rotating greater than 90degrees. At least one locking protrusion 476 may include a first portionhaving a wide engagement slit and a second portion having a narrowerengagement slit.

Because the cap preferably is configured to be disposable and the pumppreferably is configured to be reusable, the cap and pump may bedesigned such that the material of the pump housing has a greater creepresistance than the material of the cap housing. Therefore, if the forcefrom the cartridge becomes too great, the cap may be designed to fail,or deform, before the pump fails or deforms. For example, the materialof pump housing 302 may be different than the material of cap housing402. Additionally or alternatively, the material of pump housing 302 mayhave a greater thickness than the material of cap housing 402. The sameprinciple may apply to the pad. Because the pad preferably is configuredto be disposable and the pump preferably is configured to be reusable,the pad and pump may be designed such that the material of the pumphousing has a greater creep resistance than the material of the padskeleton.

With respect to FIG. 41 , a preferred embodiment of a cartridge isdescribed. The patch pump may include a pre-filled cartridge that isconfigured to be inserted into the patch pump. Cartridge 500 may befilled during manufacturing or may instead be filled by the wearer priorto inserting cartridge 500 into the pump. For example, the wearer maypre-fill several cartridges configured to last one month and store thepre-filled cartridges in the fridge until the cartridge are to be used.Preferably the wearer may insert the pre-filled cartridges into thepatch pump directly after removal from the fridge and need not wait acertain period of time (e.g., 20 minutes) before inserting thecartridge. Preferably, the pre-filled cartridge includes a movable endthat is configured to interact with the pusher of the pump and a capthat is configured to interact with the inflow needle of the cap. Forexample, the wearer may insert cartridge 500 into the pump. Cartridge500 may be sized and shaped such that when the pump and cap are coupledtogether, forming the patch pump, cartridge 500 is completely enclosedby the patch pump. Preferably, cartridge 500 contains insulin and ispre-filled with an amount of insulin that is sufficient for the wearerfor at least three days. Cartridge 500 may be a commercially availableinsulin container such as the NovoRapid PumpCart available from NovoNordisk A/S of Bagsværd, Denmark.

Cartridge 500 further may include cartridge cap 504, which may bedisposed at a first end of cartridge 500. Cartridge cap 504 may beconfigured to be inserted within the patch pump such that the inflowneedle of the cap pierces cartridge cap 504 when the cap is coupled tothe pump. Cartridge 500 further may include plunger 502, which may bedisposed at a second end of cartridge 500, the second end opposite thefirst end, and may be configured to be inserted within the patch pumpsuch that plunger 502 is disposed adjacent to the cartridge contactor ofpusher. Upon movement of the cartridge contactor, plunger 502 preferablyis configured to move towards cartridge cap 504 such that the medicationwith cartridge 500 is pushed into the inflow needle and towards themicrodosing system of the cap. When cartridge 500 is emptied, the pushermay reset to an initial, home position and cartridge 500 may be removedand replaced with another pre-filled cartridge.

Referring now to FIG. 42 , charging system 600 suitable for use with thepumps of the present invention is described and may be used to chargeone or more batteries within the pump. Preferably, charging system 600charges the battery via an inductive coil disposed within the housing ofcharger 602 and the pump. Charger 602 may be plugged into a conventionalsocket. via cable 606 or a cord with an AC or DC power converter.Charging system 600 also may include charger support frame 604, which isconfigured to hold the pump while charging. Charger support frame 604may be have a similar size and shape as the pad skeleton.

Referring now to FIG. 43A-G, illustrative screenshots of an exemplarymobile device and mobile application interfaces are described. The patchpump may be configured to communicate data to or from a mobile devicerunning software application 700 such that the user may review the dataand may activate the pump. Software application 700 may be a dedicatedapplication or “app” and may be downloaded from an online store such asiTunes™ (Apple, Inc., Cupertino, Calif.), the App Store (Apple, Inc.),Google™ Play (Google, Inc., Mountain View, Calif), the Android™Marketplace (Google, Inc.), Windows™ Phone Store (Microsoft Corp.,Redmond, Wash.), or BlackBerry™ World (BlackBerry, Waterloo, Ontario,Canada). Preferably, software application 700 need only be downloadedonce, although updates also may be downloaded.

In FIG. 43B, interface 702 permits the user to select which of variouspumps to control, with one or more icons depicting a type of pump. Thewearer may choose the icon identifying the pump that the wearer isusing. Upon identification of the type of pump, software application 700may display activation interface 704, as in FIG. 43C. Activationinterface 704 may include an “activate”, “go”, “run”, “start”, or othersimilar button or icon that the wearer may press to activate the pump.After activation of the pump, the pump may complete an initializationprocess to increase the pressure within the cartridge until it is withina predetermined range, as described above. The wearer may view thestatus of the initialization process on initialization interface 706, asin FIG. 43D.

Once the pump is activated, the wearer may wish to run a test todetermine whether the pump is working properly. Software application 700may display testing interface 708, as in FIG. 43E, which may include anicon that may be pressed by the wearer. Software application 700 maycommunicate with the pump that a delivery test should be run. Forexample, the delivery test may include delivery of one microdose ofmedication. Upon completing the test, the pump may communicate withsoftware application 700 that the test was either successful orunsuccessful. If the pump ran properly during the test, test successfulinterface 710 will be displayed, as shown in FIG. 43F, indicating thatthere were no issues. If the pump detected one or more issues during thetest, test unsuccessful interface 712 will be displayed, as in FIG. 43G.Because more than one dosing cycle may be necessary to detect anocclusion due to the flexibility of the cannula, the user may runmultiple delivery tests. Testing interface 708 and interfaces 710 and712 also may include icons allowing the wearer to choose the type ofalarm that the pump may emit. For example, the wearer may choose avibrate mode such that the pump silently alerts the wearer or the wearermay choose an audible mode.

Software application 700 also may allow the user to input informationregarding the type of cartridge that is inserted into the patch pump.For example, the cartridges that may be inserted into the patch pump mayhave different concentrations of medication. Each cartridge may haveidentification information such as concentration, volume, and/ormanufacturer information that is readable by software application 700.For example, the user may scan the identification information on thecartridge (e.g., QR code, RFID, color recognition) using the device'scamera. Software application 700 may process an image obtained from thedevice's camera using, for example, image recognition software todetermine the identification information on the cartridge and then maytransmit this information to the controller. Alternatively, in someembodiments, the patch pump may automatically identify information onthe cartridge (e.g., cartridge type, concentration, etc.) without userintervention. For example, the patch pump may automatically scan theidentification information on the cartridge upon insertion of thecartridge into the pump using an optical sensor. The controller may usethe identification information of the cartridge to modify the deliveryof the medication.

While various illustrative embodiments of the invention are describedabove, it will be apparent to one skilled in the art that variouschanges and modifications may be made therein without departing from theinvention. The appended claims are intended to cover all such changesand modifications that fall within the true scope of the invention.

What is claimed is:
 1. A medication infusion device comprising: a patchpump configured to be removably adhered to a wearer's skin fordelivering doses of medication from a cartridge through a transcutaneousportion, the patch pump comprising a pump housing; a pump motor disposedwithin the pump housing, the pump motor configured to pump themedication towards the transcutaneous portion; a sensor configured tosense a parameter; a vibration motor separate from the pump motor; and acontroller operatively coupled to the sensor and the vibration motor,the controller configured to cause the vibration motor to vibrate toalert the wearer based at least in part on the parameter sensed by thesensor.
 2. The medication infusion device of claim 1, wherein thecontroller is configured to cause the vibration motor to vibrate whenthe sensed parameter falls outside a predetermined threshold.
 3. Themedication infusion device of claim 1, wherein the controller isconfigured to determine that an error has occurred associated withoperation of the patch pump based on the sensed parameter to cause thevibration motor to vibrate based on the determination of the error. 4.The medication infusion device of claim 1, wherein the sensor isconfigured to sense a pressure within the cartridge.
 5. The medicationinfusion device of claim 4, wherein the controller is configured tocause the vibration motor to vibrate when the pressure within thecartridge falls outside a predetermined pressure range.
 6. Themedication infusion device of claim 1, further comprising a dosing tubedisposed within the pump housing, the dosing tube configured to receivemedication from the cartridge.
 7. The medication infusion device ofclaim 6, wherein the sensor is configured to detect an occlusion withinthe dosing tube or the transcutaneous portion.
 8. The medicationinfusion device of claim 7, wherein the controller is configured tocause the vibration motor to vibrate when the sensor detects informationindicative of the occlusion within the dosing tube or the transcutaneousportion.
 9. The medication infusion device of claim 7, wherein thecontroller is configured to cause the vibration motor to vibrate whenthe sensor detects repeated occlusions.
 10. The medication infusiondevice of claim 1, wherein the sensor is configured to monitor glucoselevels of the wearer.
 11. The medication infusion device of claim 10,wherein the controller is configured to cause the vibration motor tovibrate when the wearer's glucose level falls outside a predeterminedglucose level range.
 12. The medication infusion device of claim 1,wherein the sensor is disposed in a housing separate from the pumphousing.
 13. The medication infusion device of claim 1, wherein thesensor includes a photoplethysmographic module configured to sense atleast one of the wearer's heart rate or physiologic parameters.
 14. Themedication infusion device of claim 13, wherein the controller isconfigured to cause the vibration motor to vibrate when the at least oneof the wearer's heart rate or physiologic parameters fall outside apredetermined photoplethysmographic threshold.
 15. The medicationinfusion device of claim 1, wherein the sensor is an accelerometer andthe sensed parameter is associated with the wearer's activity level. 16.The medication infusion device of claim 15, wherein the controller isconfigured to cause the vibration motor to vibrate when the wearer'sactivity level is outside a predetermined threshold.
 17. The medicationinfusion device of claim 1, wherein the sensor is configured to detect atemperature within the patch pump.
 18. The medication infusion device ofclaim 17, wherein the controller is configured to cause the vibrationmotor to vibrate when the temperature falls outside a predeterminedrange.
 19. A method for using a medication infusion device, the methodcomprising: providing a patch pump configured to be removably adhered toa wearer's skin for delivering doses of medication from a cartridgethrough a transcutaneous portion, the patch pump comprising a pumphousing and a pump motor disposed within the pump housing, the pumpmotor configured to pump the medication towards the transcutaneousportion, the patch pump further comprising a vibration motor separatefrom the pump motor; sensing a parameter using a sensor; and causing thevibration motor to vibrate to alert the wearer based at least in part onthe parameter sensed by the sensor.
 20. The method of claim 1, whereincausing the vibration motor to vibrate comprises causing the vibrationmotor to vibrate when the sensed parameter falls outside a predeterminedthreshold.